INDICATIONS
TANZEUM IS INDICATED AS AN ADJUNCT TO DIET AND EXERCISE TO IMPROVE GLYCEMIC CONTROL IN ADULTS WITH TYPE 2 DIABETES MELLITUS [SEE CLINICAL STUDIES].
LIMITATIONS OF USE
" TANZEUM IS NOT RECOMMENDED AS FIRST-LINE THERAPY FOR PATIENTS INADEQUATELY CONTROLLED ON DIET AND EXERCISE BECAUSE OF THE UNCERTAIN RELEVANCE OF THE RODENT C-CELL TUMOR FINDINGS TO HUMANS. PRESCRIBE TANZEUM ONLY TO PATIENTS FOR WHOM THE POTENTIAL BENEFITS ARE CONSIDERED TO OUTWEIGH THE POTENTIAL RISK [SEE WARNINGS AND PRECAUTIONS].
" TANZEUM HAS NOT BEEN STUDIED IN PATIENTS WITH A HISTORY OF PANCREATITIS [SEE WARNINGS AND PRECAUTIONS]. CONSIDER OTHER ANTIDIABETIC THERAPIES IN PATIENTS WITH A HISTORY OF PANCREATITIS.
" TANZEUM IS NOT INDICATED IN THE TREATMENT OF PATIENTS WITH TYPE 1 DIABETES MELLITUS OR FOR THE TREATMENT OF PATIENTS WITH DIABETIC KETOACIDOSIS. TANZEUM IS NOT A SUBSTITUTE FOR INSULIN IN THESE PATIENTS.
" TANZEUM HAS NOT BEEN STUDIED IN PATIENTS WITH SEVERE GASTROINTESTINAL DISEASE, INCLUDING SEVERE GASTROPARESIS. THE USE OF TANZEUM IS NOT RECOMMENDED IN PATIENTS WITH PRE-EXISTING SEVERE GASTROINTESTINAL DISEASE [SEE ADVERSE REACTIONS].
" TANZEUM HAS NOT BEEN STUDIED IN COMBINATION WITH PRANDIAL INSULIN.
HOW SUPPLIED
DOSAGE FORMS AND STRENGTHS
TANZEUM IS SUPPLIED AS FOLLOWS:
" FOR INJECTION: 30-MG LYOPHILIZED POWDER IN A SINGLE-DOSE PEN (PEN INJECTOR) FOR RECONSTITUTION.
" FOR INJECTION: 50-MG LYOPHILIZED POWDER IN A SINGLE-DOSE PEN (PEN INJECTOR) FOR RECONSTITUTION.
TANZEUM IS AVAILABLE IN THE FOLLOWING STRENGTHS AND PACKAGE SIZE:
30 MG SINGLE-DOSE PEN (NDC 0173-0866-01): CARTON OF 4 (CONTAINING FOUR 29-GAUGE, 5-MM, THINWALL NEEDLES): NDC 0173-0866-35
50 MG SINGLE-DOSE PEN (NDC 0173-0867-01): CARTON OF 4 (CONTAINING FOUR 29-GAUGE, 5-MM, THINWALL NEEDLES): NDC 0173-0867-35
STORAGE AND HANDLING
" PRIOR TO DISPENSING: STORE PENS IN THE REFRIGERATOR AT 36°F TO 46°F (2°C TO 8°C). PENS MAY BE STORED REFRIGERATED UNTIL THE EXPIRATION DATE.
" FOLLOWING DISPENSING: STORE PENS IN THE REFRIGERATOR AT 36°F TO 46°F (2°C TO 8°C). PATIENTS MAY STORE PENS AT ROOM TEMPERATURE NOT TO EXCEED 86°F (30°C) FOR UP TO 4 WEEKS PRIOR TO USE. STORE PENS IN THE ORIGINAL CARTON UNTIL USE.
" DO NOT FREEZE.
" DO NOT USE PAST THE EXPIRATION DATE.
" USE WITHIN 8 HOURS AFTER RECONSTITUTION.
MANUFACTURED BY GLAXOSMITHKLINE LLC, WILMINGTON, DE 19808, U.S. LIC NO. 1727. MARKETED BY GLAXOSMITHKLINE, RESEARCH TRIANGLE PARK, NC 27709. REVISED: MARCH 2015
DOSAGE AND ADMINISTRATION
DOSAGE
THE RECOMMENDED DOSAGE OF TANZEUM IS 30 MG ONCE WEEKLY GIVEN AS A SUBCUTANEOUS INJECTION IN THE ABDOMEN, THIGH, OR UPPER ARM REGION. THE DOSAGE MAY BE INCREASED TO 50 MG ONCE WEEKLY IF THE GLYCEMIC RESPONSE IS INADEQUATE.
TANZEUM MAY BE ADMINISTERED AT ANY TIME OF DAY WITHOUT REGARD TO MEALS. INSTRUCT PATIENTS TO ADMINISTER TANZEUM ONCE A WEEK ON THE SAME DAY EACH WEEK. THE DAY OF WEEKLY ADMINISTRATION MAY BE CHANGED IF NECESSARY AS LONG AS THE LAST DOSE WAS ADMINISTERED 4 OR MORE DAYS BEFORE.
IF A DOSE IS MISSED, INSTRUCT PATIENTS TO ADMINISTER AS SOON AS POSSIBLE WITHIN 3 DAYS AFTER THE MISSED DOSE. THEREAFTER, PATIENTS CAN RESUME DOSING ON THEIR USUAL DAY OF ADMINISTRATION. IF IT IS MORE THAN 3 DAYS AFTER THE MISSED DOSE, INSTRUCT PATIENTS TO WAIT UNTIL THEIR NEXT REGULARLY SCHEDULED WEEKLY DOSE.
CONCOMITANT USE WITH AN INSULIN SECRETAGOGUE (E.G., SULFONYLUREA) OR WITH INSULIN
WHEN INITIATING TANZEUM, CONSIDER REDUCING THE DOSAGE OF CONCOMITANTLY ADMINISTERED INSULIN SECRETAGOGUES (E.G., SULFONYLUREAS) OR INSULIN TO REDUCE THE RISK OF HYPOGLYCEMIA [SEE WARNINGS AND PRECAUTIONS].
DOSAGE IN PATIENTS WITH RENAL IMPAIRMENT
NO DOSE ADJUSTMENT IS NEEDED IN PATIENTS WITH MILD, MODERATE, OR SEVERE RENAL IMPAIRMENT (EGFR 15 TO 89 ML/MIN/1.73 M²). USE CAUTION WHEN INITIATING OR ESCALATING DOSES OF TANZEUM IN PATIENTS WITH RENAL IMPAIRMENT. MONITOR RENAL FUNCTION IN PATIENTS WITH RENAL IMPAIRMENT REPORTING SEVERE ADVERSE GASTROINTESTINAL REACTIONS [SEE WARNINGS AND PRECAUTIONS, USE IN SPECIFIC POPULATIONS].
RECONSTITUTION OF THE LYOPHILIZED POWDER
THE LYOPHILIZED POWDER CONTAINED WITHIN THE PEN MUST BE RECONSTITUTED PRIOR TO ADMINISTRATION. SEE PATIENT INSTRUCTIONS FOR USE FOR COMPLETE ADMINISTRATION INSTRUCTIONS WITH ILLUSTRATIONS. THE INSTRUCTIONS MAY ALSO BE FOUND AT WWW.TANZEUM.COM. INSTRUCT PATIENTS AS FOLLOWS:
PEN RECONSTITUTION
A) HOLD THE PEN BODY WITH THE CLEAR CARTRIDGE POINTING UP TO SEE THE [1] IN THE NUMBER WINDOW.
B) TO RECONSTITUTE THE LYOPHILIZED POWDER WITH THE DILUENT IN THE PEN, TWIST THE CLEAR CARTRIDGE ON THE PEN IN THE DIRECTION OF THE ARROW UNTIL THE PEN IS FELT/HEARD TO "CLICK" INTO PLACE AND THE [2] IS SEEN IN THE NUMBER WINDOW. THIS MIXES THE DILUENT WITH THE LYOPHILIZED POWDER.
C) SLOWLY AND GENTLY ROCK THE PEN SIDE-TO-SIDE 5 TIMES TO MIX THE RECONSTITUTED SOLUTION OF TANZEUM. ADVISE THE PATIENT TO NOT SHAKE THE PEN HARD TO AVOID FOAMING.
D) WAIT 15 MINUTES FOR THE 30-MG PEN AND 30 MINUTES FOR THE 50-MG PEN TO ENSURE THAT THE RECONSTITUTED SOLUTION IS MIXED.
PREPARING PEN FOR INJECTION
E) SLOWLY AND GENTLY ROCK THE PEN SIDE-TO-SIDE 5 ADDITIONAL TIMES TO MIX THE RECONSTITUTED SOLUTION.
F) VISUALLY INSPECT THE RECONSTITUTED SOLUTION IN THE VIEWING WINDOW FOR PARTICULATE MATTER. THE RECONSTITUTED SOLUTION WILL BE YELLOW IN COLOR. AFTER RECONSTITUTION, USE TANZEUM WITHIN 8 HOURS.
G) HOLDING THE PEN UPRIGHT, ATTACH THE NEEDLE TO THE PEN. GENTLY TAP THE CLEAR CARTRIDGE TO BRING LARGE BUBBLES TO THE TOP.
SEE DOSAGE AND ADMINISTRATION FOR IMPORTANT ADMINISTRATION INSTRUCTIONS, INCLUDING THE INJECTION PROCEDURE.
ALTERNATE METHOD OF RECONSTITUTION (HEALTHCARE PROFESSIONAL USE ONLY)
THE PATIENT INSTRUCTIONS FOR USE PROVIDE DIRECTIONS FOR THE PATIENT TO WAIT 15 MINUTES FOR THE 30-MG PEN AND 30 MINUTES FOR THE 50-MG PEN AFTER THE LYOPHILIZED POWDER AND DILUENT ARE MIXED TO ENSURE RECONSTITUTION.
HEALTHCARE PROFESSIONALS MAY UTILIZE THE FOLLOWING ALTERNATE METHOD OF RECONSTITUTION. BECAUSE THIS METHOD RELIES ON APPROPRIATE SWIRLING AND VISUAL INSPECTION OF THE SOLUTION, IT SHOULD ONLY BE PERFORMED BY HEALTHCARE PROFESSIONALS.
a. FOLLOW STEP A (INSPECT YOUR PEN AND MIX YOUR MEDICATION) IN THE INSTRUCTIONS FOR USE. MAKE SURE YOU HAVE:
o INSPECTED THE PEN FOR [1] IN THE NUMBER WINDOW AND EXPIRATION DATE.
o TWISTED THE CLEAR CARTRIDGE UNTIL [2] APPEARS IN THE NUMBER WINDOW AND A "CLICK" IS HEARD. THIS COMBINES THE MEDICINE POWDER AND LIQUID IN THE CLEAR CARTRIDGE.
b. HOLD THE PEN WITH THE CLEAR CARTRIDGE POINTING UP AND MAINTAIN THIS ORIENTATION THROUGHOUT THE RECONSTITUTION.
c. GENTLY SWIRL THE PEN IN SMALL CIRCULAR MOTIONS FOR AT LEAST ONE MINUTE. AVOID SHAKING AS THIS CAN RESULT IN FOAMING, WHICH MAY AFFECT THE DOSE.
d. INSPECT THE SOLUTION, AND IF NEEDED, CONTINUE TO GENTLY SWIRL THE PEN UNTIL ALL THE POWDER IS DISSOLVED AND YOU SEE A CLEAR YELLOW SOLUTION THAT IS FREE OF PARTICLES. A SMALL AMOUNT OF FOAM, ON TOP OF THE SOLUTION AT THE END OF RECONSTITUTION, IS NORMAL.
o FOR 30-MG PEN: COMPLETE DISSOLUTION USUALLY OCCURS WITHIN 2 MINUTES BUT MAY TAKE UP TO 5 MINUTES, AS CONFIRMED BY VISUAL INSPECTION FOR A CLEAR YELLOW SOLUTION FREE OF PARTICLES.
o FOR 50-MG PEN: COMPLETE DISSOLUTION USUALLY OCCURS WITHIN 7 MINUTES BUT MAY TAKE UP TO 10 MINUTES.
e. AFTER RECONSTITUTION, CONTINUE TO FOLLOW THE STEPS IN THE INSTRUCTIONS FOR USE, STARTING AT STEP B: ATTACH THE NEEDLE.
IMPORTANT ADMINISTRATION INSTRUCTIONS
INSTRUCT PATIENTS AS FOLLOWS:
" THE PEN SHOULD BE USED WITHIN 8 HOURS OF RECONSTITUTION PRIOR TO ATTACHING THE NEEDLE.
" AFTER ATTACHING THE SUPPLIED NEEDLE, REMOVE AIR BUBBLES BY SLOWLY TWISTING THE PEN UNTIL YOU SEE THE [3] IN THE NUMBER WINDOW. AT THE SAME TIME, THE INJECTION BUTTON WILL BE AUTOMATICALLY RELEASED FROM THE BOTTOM OF THE PEN.
" USE IMMEDIATELY AFTER THE NEEDLE IS ATTACHED AND PRIMED. THE PRODUCT CAN CLOG THE NEEDLE IF ALLOWED TO DRY IN THE PRIMED NEEDLE.
" AFTER SUBCUTANEOUSLY INSERTING THE NEEDLE INTO THE SKIN IN THE ABDOMEN, THIGH, OR UPPER ARM REGION, PRESS THE INJECTION BUTTON. HOLD THE INJECTION BUTTON UNTIL YOU HEAR A "CLICK" AND THEN HOLD THE BUTTON FOR 5 ADDITIONAL SECONDS TO DELIVER THE FULL DOSE.
WHEN USING TANZEUM WITH INSULIN, INSTRUCT PATIENTS TO ADMINISTER AS SEPARATE INJECTIONS AND TO NEVER MIX THE PRODUCTS. IT IS ACCEPTABLE TO INJECT TANZEUM AND INSULIN IN THE SAME BODY REGION BUT THE INJECTIONS SHOULD NOT BE ADJACENT TO EACH OTHER.
WHEN INJECTING IN THE SAME BODY REGION, ADVISE PATIENTS TO USE A DIFFERENT INJECTION SITE EACH WEEK. TANZEUM MUST NOT BE ADMINISTERED INTRAVENOUSLY OR INTRAMUSCULARLY.
SIDE EFFECTS
THE FOLLOWING SERIOUS REACTIONS ARE DESCRIBED BELOW OR ELSEWHERE IN THE PRESCRIBING INFORMATION:
" RISK OF THYROID C-CELL TUMORS [SEE WARNINGS AND PRECAUTIONS]
" ACUTE PANCREATITIS [SEE WARNINGS AND PRECAUTIONS]
" HYPOGLYCEMIA WITH CONCOMITANT USE OF INSULIN SECRETAGOGUES OR INSULIN [SEE WARNINGS AND PRECAUTIONS]
" HYPERSENSITIVITY REACTIONS [SEE WARNINGS AND PRECAUTIONS]
" RENAL IMPAIRMENT [SEE WARNINGS AND PRECAUTIONS]
CLINICAL TRIALS EXPERIENCE
BECAUSE CLINICAL TRIALS ARE CONDUCTED UNDER WIDELY VARYING CONDITIONS, ADVERSE REACTION RATES OBSERVED IN THE CLINICAL TRIALS OF A DRUG CANNOT BE DIRECTLY COMPARED WITH RATES IN THE CLINICAL TRIALS OF ANOTHER DRUG AND MAY NOT REFLECT THE RATES OBSERVED IN PRACTICE.
POOL OF PLACEBO-CONTROLLED TRIALS
THE DATA IN TABLE 1 ARE DERIVED FROM 4 PLACEBO-CONTROLLED TRIALS. TANZEUM WAS USED AS MONOTHERAPY IN 1 TRIAL AND AS ADD-ON THERAPY IN 3 TRIALS [SEE CLINICAL STUDIES]. THESE DATA REFLECT EXPOSURE OF 923 PATIENTS TO TANZEUM AND A MEAN DURATION OF EXPOSURE TO TANZEUM OF 93 WEEKS. THE MEAN AGE OF PARTICIPANTS WAS 55 YEARS, 1% OF PARTICIPANTS WERE 75 YEARS OR OLDER AND 53% OF PARTICIPANTS WERE MALE. THE POPULATION IN THESE STUDIES WAS 48% WHITE, 13% AFRICAN/AFRICAN AMERICAN, 7% ASIAN, AND 29% HISPANIC/LATINO. AT BASELINE, THE POPULATION HAD DIABETES FOR AN AVERAGE OF 7 YEARS AND HAD A MEAN HBA1C OF 8.1%. AT BASELINE, 17% OF THE POPULATION IN THESE STUDIES REPORTED PERIPHERAL NEUROPATHY AND 4% REPORTED RETINOPATHY. BASELINE ESTIMATED RENAL FUNCTION WAS NORMAL OR MILDLY IMPAIRED (EGFR > 60 ML/MIN/1.73 M²) IN 91% OF THE STUDY POPULATION AND MODERATELY IMPAIRED (EGFR 30 TO 60 ML/MIN/1.73 M²) IN 9%.
TABLE 1 SHOWS COMMON ADVERSE REACTIONS EXCLUDING HYPOGLYCEMIA ASSOCIATED WITH THE USE OF TANZEUM IN THE POOL OF PLACEBO-CONTROLLED TRIALS. THESE ADVERSE REACTIONS WERE NOT PRESENT AT BASELINE, OCCURRED MORE COMMONLY ON TANZEUM THAN ON PLACEBO, AND OCCURRED IN AT LEAST 5% OF PATIENTS TREATED WITH TANZEUM.
TABLE 1: ADVERSE REACTIONS IN PLACEBO-CONTROLLED TRIALS REPORTED IN ? 5% OF PATIENTS TREATED WITH TANZEUMA
ADVERSE REACTION PLACEBO
(N = 468)% TANZEUM
(N = 923)%
UPPER RESPIRATORY TRACT INFECTION 13.0 14.2
DIARRHEA 10.5 13.1
NAUSEA 9.6 11.1
INJECTION SITE REACTIONB 2.1 10.5
COUGH 6.2 6.9
BACK PAIN 5.8 6.7
ARTHRALGIA 6.4 6.6
SINUSITIS 5.8 6.2
INFLUENZA 3.2 5.2
A ADVERSE REACTIONS REPORTED INCLUDES ADVERSE REACTIONS OCCURRING WITH THE USE OF GLYCEMIC RESCUE MEDICATIONS WHICH INCLUDED METFORMIN (17% FOR PLACEBO AND 10% FOR TANZEUM) AND INSULIN (24% FOR PLACEBO AND 14% FOR TANZEUM).
B SEE BELOW FOR OTHER EVENTS OF INJECTION SITE REACTIONS REPORTED.
GASTROINTESTINAL ADVERSE REACTIONS
IN THE POOL OF PLACEBO-CONTROLLED TRIALS, GASTROINTESTINAL COMPLAINTS OCCURRED MORE FREQUENTLY AMONG PATIENTS RECEIVING TANZEUM (39%) THAN PATIENTS RECEIVING PLACEBO (33%). IN ADDITION TO DIARRHEA AND NAUSEA (SEE TABLE 1), THE FOLLOWING GASTROINTESTINAL ADVERSE REACTIONS ALSO OCCURRED MORE FREQUENTLY IN PATIENTS RECEIVING TANZEUM: VOMITING (2.6% VERSUS 4.2% FOR PLACEBO VERSUS TANZEUM), GASTROESOPHAGEAL REFLUX DISEASE (1.9% VERSUS 3.5% FOR PLACEBO VERSUS TANZEUM), AND DYSPEPSIA (2.8% VERSUS 3.4% FOR PLACEBO VERSUS TANZEUM). CONSTIPATION ALSO CONTRIBUTED TO THE FREQUENTLY REPORTED REACTIONS. IN THE GROUP TREATED WITH TANZEUM, INVESTIGATORS GRADED THE SEVERITY OF GI REACTIONS AS "MILD" IN 56% OF CASES, "MODERATE" IN 37% OF CASES, AND "SEVERE" IN 7% OF CASES. DISCONTINUATION DUE TO GI ADVERSE REACTIONS OCCURRED IN 2% OF INDIVIDUALS ON TANZEUM OR PLACEBO.
INJECTION SITE REACTIONS
IN THE POOL OF PLACEBO-CONTROLLED TRIALS, INJECTION SITE REACTIONS OCCURRED MORE FREQUENTLY ON TANZEUM (18%) THAN ON PLACEBO (8%). IN ADDITION TO THE TERM INJECTION SITE REACTION (SEE TABLE 1), THE FOLLOWING OTHER TYPES OF INJECTION SITE REACTIONS ALSO OCCURRED MORE FREQUENTLY ON TANZEUM: INJECTION SITE HEMATOMA (1.9% VERSUS 2.1% FOR PLACEBO VERSUS TANZEUM ), INJECTION SITE ERYTHEMA (0.4% VERSUS 1.7% FOR PLACEBO VERSUS TANZEUM), INJECTION SITE RASH (0% VERSUS 1.4% FOR PLACEBO VERSUS TANZEUM), INJECTION SITE HYPERSENSITIVITY (0% VERSUS 0.8% FOR PLACEBO VERSUS TANZEUM), AND INJECTION SITE HEMORRHAGE (0.6% VERSUS 0.7% FOR PLACEBO VERSUS TANZEUM). INJECTION SITE PRURITUS ALSO CONTRIBUTED TO THE FREQUENTLY REPORTED REACTIONS. THE MAJORITY OF INJECTION SITE REACTIONS WERE JUDGED AS "MILD" BY INVESTIGATORS IN BOTH GROUPS (73% FOR TANZEUM VERSUS 94% FOR PLACEBO). MORE PATIENTS ON TANZEUM THAN ON PLACEBO: DISCONTINUED DUE TO AN INJECTION SITE REACTION (2% VERSUS 0.2%), EXPERIENCED MORE THAN 2 REACTIONS (38% VERSUS 20%), HAD A REACTION JUDGED BY INVESTIGATORS TO BE "MODERATE" OR "SEVERE" (27% VERSUS 6%) AND REQUIRED LOCAL OR SYSTEMIC TREATMENT FOR THE REACTIONS (36% VERSUS 11%).
POOL OF PLACEBO- AND ACTIVE-CONTROLLED TRIALS
THE OCCURRENCE OF ADVERSE REACTIONS WAS ALSO EVALUATED IN A LARGER POOL OF PATIENTS WITH TYPE 2 DIABETES PARTICIPATING IN 7 PLACEBO- AND ACTIVE-CONTROLLED TRIALS. THESE TRIALS EVALUATED THE USE OF TANZEUM AS MONOTHERAPY, AND AS ADD-ON THERAPY TO ORAL ANTIDIABETIC AGENTS, AND AS ADD-ON THERAPY TO BASAL INSULIN [SEE CLINICAL STUDIES]. IN THIS POOL, A TOTAL OF 2,116 PATIENTS WITH TYPE 2 DIABETES WERE TREATED WITH TANZEUM FOR A MEAN DURATION OF 75 WEEKS. THE MEAN AGE OF PATIENTS TREATED WITH TANZEUM WAS 55 YEARS, 1.5% OF THE POPULATION IN THESE STUDIES WAS 75 YEARS OR OLDER AND 51% OF PARTICIPANTS WERE MALE. FORTY-EIGHT PERCENT OF PATIENTS WERE WHITE, 15% AFRICAN/AFRICAN AMERICAN, 9% ASIAN, AND 26% WERE HISPANIC/LATINO. AT BASELINE, THE POPULATION HAD DIABETES FOR AN AVERAGE OF 8 YEARS AND HAD A MEAN HBA1C OF 8.2%. AT BASELINE, 21% OF THE POPULATION REPORTED PERIPHERAL NEUROPATHY AND 5% REPORTED RETINOPATHY. BASELINE ESTIMATED RENAL FUNCTION WAS NORMAL OR MILDLY IMPAIRED (EGFR > 60 ML/MIN/1.73 M²) IN 92% OF THE POPULATION AND MODERATELY IMPAIRED (EGFR 30 TO 60 ML/MIN/1.73 M²) IN 8% OF THE POPULATION.
IN THE POOL OF PLACEBO- AND ACTIVE-CONTROLLED TRIALS, THE TYPES AND FREQUENCY OF COMMON ADVERSE REACTIONS EXCLUDING HYPOGLYCEMIA WERE SIMILAR TO THOSE LISTED IN TABLE 1.
OTHER ADVERSE REACTIONS
HYPOGLYCEMIA
THE PROPORTION OF PATIENTS EXPERIENCING AT LEAST ONE DOCUMENTED SYMPTOMATIC HYPOGLYCEMIC EPISODE ON TANZEUM AND THE PROPORTION OF PATIENTS EXPERIENCING AT LEAST ONE SEVERE HYPOGLYCEMIC EPISODE ON TANZEUM IN CLINICAL TRIALS [SEE CLINICAL STUDIES] IS SHOWN IN TABLE 2. HYPOGLYCEMIA WAS MORE FREQUENT WHEN TANZEUM WAS ADDED TO SULFONYLUREA OR INSULIN [SEE WARNINGS AND PRECAUTIONS].
TABLE 2: INCIDENCE (%) OF HYPOGLYCEMIA IN CLINICAL TRIALS OF TANZEUMA
MONOTHERAPYB(52 WEEKS) PLACEBO
N = 101 TANZEUM 30 MG WEEKLY
N = 101
DOCUMENTED SYMPTOMATICC 2% 2%
SEVERED - -
IN COMBINATION WITH METFORMIN TRIAL (104 WEEKS)E PLACEBO
N = 101 TANZEUM
N = 302
DOCUMENTED SYMPTOMATIC 4% 3%
SEVERE - -
IN COMBINATION WITH PIOGLITAZONE ± METFORMIN (52 WEEKS) PLACEBO
N = 151 TANZEUM
N = 150
DOCUMENTED SYMPTOMATIC 1% 3%
SEVERE - 1%
IN COMBINATION WITH METFORMIN AND SULFONYLUREA (52 WEEKS) PLACEBO
N = 115 TANZEUM
N = 271
DOCUMENTED SYMPTOMATIC 7% 13%
SEVERE - 0.4%
IN COMBINATION WITH INSULIN GLARGINE (26 WEEKS) INSULIN LISPRO
N = 281 TANZEUM
N = 285
DOCUMENTED SYMPTOMATIC 30% 16%
SEVERE 0.7% -
IN COMBINATION WITH METFORMIN ± SULFONYLUREA (52 WEEKS) INSULIN GLARGINE
N = 241 TANZEUM
N = 504
DOCUMENTED SYMPTOMATIC 27% 17%
SEVERE 0.4% 0.4%
IN COMBINATION WITH OADS IN RENAL IMPAIRMENT (26 WEEKS) SITAGLIPTIN
N = 246 TANZEUM
N = 249
DOCUMENTED SYMPTOMATIC 6% 10%
SEVERE 0.8% -
OAD = ORAL ANTIDIABETIC AGENTS.
A DATA PRESENTED ARE TO THE PRIMARY ENDPOINT AND INCLUDE ONLY EVENTS OCCURRING ON-THERAPY WITH RANDOMIZED MEDICATIONS AND EXCLUDES EVENTS OCCURRING AFTER USE OF GLYCEMIC RESCUE MEDICATIONS (I.E., PRIMARILY METFORMIN OR INSULIN).
B IN THIS TRIAL, NO DOCUMENTED SYMPTOMATIC OR SEVERE HYPOGLYCEMIA WERE REPORTED FOR TANZEUM 50 MG AND THESE DATA ARE OMITTED FROM THE TABLE.
C PLASMA GLUCOSE CONCENTRATION ? 70 MG/DL AND PRESENCE OF HYPOGLYCEMIC SYMPTOMS.
D EVENT REQUIRING ANOTHER PERSON TO ADMINISTER A RESUSCITATIVE ACTION.
E RATE OF DOCUMENTED SYMPTOMATIC HYPOGLYCEMIA FOR ACTIVE CONTROLS 18% (GLIMEPIRIDE) AND 2% (SITAGLIPTIN).
PNEUMONIA
IN THE POOL OF 7 PLACEBO- AND ACTIVE-CONTROLLED TRIALS, THE ADVERSE REACTION OF PNEUMONIA WAS REPORTED MORE FREQUENTLY IN PATIENTS RECEIVING TANZEUM (1.8%) THAN IN PATIENTS IN THE ALL-COMPARATORS GROUP (0.8%). MORE CASES OF PNEUMONIA IN THE GROUP RECEIVING TANZEUM WERE SERIOUS (0.4% FOR TANZEUM VERSUS 0.1% FOR ALL COMPARATORS).
ATRIAL FIBRILLATION/FLUTTER
IN THE POOL OF 7 PLACEBO- AND ACTIVE-CONTROLLED TRIALS, ADVERSE REACTIONS OF ATRIAL FIBRILLATION (1.0%) AND ATRIAL FLUTTER (0.2%) WERE REPORTED MORE FREQUENTLY FOR TANZEUM THAN FOR ALL COMPARATORS (0.5% AND 0%, RESPECTIVELY). IN BOTH GROUPS, PATIENTS WITH EVENTS WERE GENERALLY MALE, OLDER, AND HAD UNDERLYING RENAL IMPAIRMENT OR CARDIAC DISEASE (E.G., HISTORY OF ARRHYTHMIA, PALPITATIONS, CONGESTIVE HEART FAILURE, CARDIOMYOPATHY, ETC.).
APPENDICITIS
IN THE POOL OF PLACEBO- AND ACTIVE-CONTROLLED TRIALS, SERIOUS EVENTS OF APPENDICITIS OCCURRED IN 0.3% OF PATIENTS TREATED WITH TANZEUM COMPARED WITH 0% AMONG ALL COMPARATORS.
IMMUNOGENICITY
IN THE POOL OF 7 PLACEBO- AND ACTIVE-CONTROLLED TRIALS, 116 (5.5%) OF 2,098 PATIENTS EXPOSED TO TANZEUM TESTED POSITIVE FOR ANTI-ALBIGLUTIDE ANTIBODIES AT ANY TIME DURING THE TRIALS. NONE OF THESE ANTIBODIES WERE SHOWN TO NEUTRALIZE THE ACTIVITY OF ALBIGLUTIDE IN AN IN VITRO BIOASSAY. PRESENCE OF ANTIBODY DID NOT CORRELATE WITH REDUCED EFFICACY AS MEASURED BY HBA1C AND FASTING PLASMA GLUCOSE OR SPECIFIC ADVERSE REACTIONS.
CONSISTENT WITH THE HIGH HOMOLOGY OF ALBIGLUTIDE WITH HUMAN GLP-1, THE MAJORITY OF PATIENTS (APPROXIMATELY 79%) WITH ANTI-ALBIGLUTIDE ANTIBODIES ALSO TESTED POSITIVE FOR ANTI-GLP-1 ANTIBODIES; NONE WERE NEUTRALIZING. A MINORITY OF PATIENTS (APPROXIMATELY 17%) WHO TESTED POSITIVE FOR ANTI-ALBIGLUTIDE ANTIBODIES ALSO TRANSIENTLY TESTED POSITIVE FOR ANTIBODIES TO HUMAN ALBUMIN.
THE DETECTION OF ANTIBODY FORMATION IS HIGHLY DEPENDENT ON THE SENSITIVITY AND SPECIFICITY OF THE ASSAY. ADDITIONALLY, THE OBSERVED INCIDENCE OF ANTIBODY (INCLUDING NEUTRALIZING ANTIBODY) POSITIVITY IN AN ASSAY MAY BE INFLUENCED BY SEVERAL FACTORS INCLUDING ASSAY METHODOLOGY, SAMPLE HANDLING, TIMING OF SAMPLE COLLECTION, CONCOMITANT MEDICATIONS, AND UNDERLYING DISEASE. FOR THESE REASONS, THE INCIDENCE OF ANTIBODIES TO ALBIGLUTIDE CANNOT BE DIRECTLY COMPARED WITH THE INCIDENCE OF ANTIBODIES OF OTHER PRODUCTS.
LIVER ENZYME ABNORMALITIES
IN THE POOL OF PLACEBO- AND ACTIVE-CONTROLLED TRIALS, A SIMILAR PROPORTION OF PATIENTS EXPERIENCED AT LEAST ONE EVENT OF ALANINE AMINOTRANSFERASE (ALT) INCREASE OF 3-FOLD OR GREATER ABOVE THE UPPER LIMIT OF NORMAL (0.9% AND 0.9% FOR ALL COMPARATORS VERSUS TANZEUM). THREE SUBJECTS ON TANZEUM AND ONE SUBJECT IN THE ALL-COMPARATOR GROUP EXPERIENCED AT LEAST ONE EVENT OF ALT INCREASE OF 10-FOLD OR GREATER ABOVE THE UPPER LIMIT OF NORMAL. IN ONE OF THE 3 CASES AN ALTERNATE ETIOLOGY WAS IDENTIFIED TO EXPLAIN THE RISE IN LIVER ENZYME (ACUTE VIRAL HEPATITIS). IN ONE CASE, INSUFFICIENT INFORMATION WAS OBTAINED TO ESTABLISH OR REFUTE A DRUG-RELATED CAUSALITY. IN THE THIRD CASE, ELEVATION IN ALT (10 TIMES THE UPPER LIMIT OF NORMAL) WAS ACCOMPANIED BY AN INCREASE IN TOTAL BILIRUBIN (4 TIMES THE UPPER LIMIT OF NORMAL) AND OCCURRED 8 DAYS AFTER THE FIRST DOSE OF TANZEUM. THE ETIOLOGY OF HEPATOCELLULAR INJURY WAS POSSIBLY RELATED TO TANZEUM BUT DIRECT ATTRIBUTION TO TANZEUM WAS CONFOUNDED BY THE PRESENCE OF GALLSTONE DISEASE DIAGNOSED ON ULTRASOUND 3 WEEKS AFTER THE EVENT.
GAMMA GLUTAMYLTRANSFERASE (GGT) INCREASE
IN THE POOL OF PLACEBO-CONTROLLED TRIALS, THE ADVERSE EVENT OF INCREASED GGT OCCURRED MORE FREQUENTLY IN THE GROUP TREATED WITH TANZEUM (0.9% AND 1.5% FOR PLACEBO VERSUS TANZEUM).
HEART RATE INCREASE
IN THE POOL OF PLACEBO-CONTROLLED TRIALS, MEAN HEART RATE IN PATIENTS TREATED WITH TANZEUM WAS HIGHER BY AN AVERAGE OF 1 TO 2 BPM COMPARED WITH MEAN HEART RATE IN PATIENTS TREATED WITH PLACEBO ACROSS STUDY VISITS. THE LONG-TERM CLINICAL EFFECTS OF THE INCREASE IN HEART RATE HAVE NOT BEEN ESTABLISHED [SEE WARNINGS AND PRECAUTIONS].
READ THE TANZEUM (ALBIGLUTIDE PEN FOR INJECTION, FOR SUBCUTANEOUS USE) SIDE EFFECTS CENTER FOR A COMPLETE GUIDE TO POSSIBLE SIDE EFFECTS
OVERDOSE
NO DATA ARE AVAILABLE WITH REGARD TO OVERDOSAGE IN HUMANS. ANTICIPATED SYMPTOMS OF AN OVERDOSE MAY BE SEVERE NAUSEA AND VOMITING.
IN THE EVENT OF AN OVERDOSE, APPROPRIATE SUPPORTIVE TREATMENT SHOULD BE INITIATED AS DICTATED BY THE PATIENT'S CLINICAL SIGNS AND SYMPTOMS. A PROLONGED PERIOD OF OBSERVATION AND TREATMENT FOR THESE SYMPTOMS MAY BE NECESSARY, TAKING INTO ACCOUNT THE HALF-LIFE OF TANZEUM (5 DAYS).
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
TANZEUM IS AN AGONIST OF THE GLP-1 RECEPTOR AND AUGMENTS GLUCOSE-DEPENDENT INSULIN SECRETION. TANZEUM ALSO SLOWS GASTRIC EMPTYING.
PHARMACODYNAMICS
TANZEUM LOWERS FASTING GLUCOSE AND REDUCES POSTPRANDIAL GLUCOSE EXCURSIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS. THE MAJORITY OF THE OBSERVED REDUCTION IN FASTING PLASMA GLUCOSE OCCURS AFTER A SINGLE DOSE, CONSISTENT WITH THE PHARMACOKINETIC PROFILE OF ALBIGLUTIDE. IN A PHASE II TRIAL IN JAPANESE PATIENTS WITH TYPE 2 DIABETES MELLITUS WHO RECEIVED TANZEUM 30 MG, A REDUCTION (22%) IN POSTPRANDIAL GLUCOSE AUC(0-3 H) WAS OBSERVED AT STEADY STATE (WEEK 16) COMPARED WITH PLACEBO FOLLOWING A MIXED MEAL.
A SINGLE DOSE OF TANZEUM 50 MG SUBCUTANEOUS (SC) DID NOT IMPAIR GLUCAGON RESPONSE TO LOW GLUCOSE CONCENTRATIONS.
GASTRIC MOTILITY
TANZEUM SLOWED GASTRIC EMPTYING COMPARED WITH PLACEBO FOR BOTH SOLIDS AND LIQUIDS WHEN ALBIGLUTIDE 100 MG (2 TIMES THE MAXIMUM APPROVED DOSAGE) WAS ADMINISTERED AS A SINGLE DOSE IN HEALTHY SUBJECTS.
CARDIAC ELECTROPHYSIOLOGY
AT DOSES UP TO THE MAXIMUM RECOMMENDED DOSE (50 MG), TANZEUM DOES NOT PROLONG QTC TO ANY CLINICALLY RELEVANT EXTENT.
PHARMACOKINETICS
ABSORPTION
FOLLOWING SC ADMINISTRATION OF A SINGLE 30-MG DOSE TO SUBJECTS WITH TYPE 2 DIABETES MELLITUS, MAXIMUM CONCENTRATIONS OF ALBIGLUTIDE WERE REACHED AT 3 TO 5 DAYS POST-DOSING. THE MEAN PEAK CONCENTRATION (CMAX) AND MEAN AREA UNDER THE TIME-CONCENTRATION CURVE (AUC) OF ALBIGLUTIDE WERE 1.74 MCG/ML AND 465 MCG.H/ML, RESPECTIVELY, FOLLOWING A SINGLE DOSE OF 30 MG ALBIGLUTIDE IN TYPE 2 DIABETES MELLITUS SUBJECTS. STEADY-STATE EXPOSURES ARE ACHIEVED FOLLOWING 4 TO 5 WEEKS OF ONCE-WEEKLY ADMINISTRATION. EXPOSURES AT THE 30-MG AND 50-MG DOSE LEVELS WERE CONSISTENT WITH A DOSE-PROPORTIONAL INCREASE. SIMILAR EXPOSURE IS ACHIEVED WITH SC ADMINISTRATION OF ALBIGLUTIDE IN THE ABDOMEN, THIGH, OR UPPER ARM. THE ABSOLUTE BIOAVAILABILITY OF ALBIGLUTIDE FOLLOWING SC ADMINISTRATION HAS NOT BEEN EVALUATED.
DISTRIBUTION
THE MEAN ESTIMATE OF APPARENT VOLUME OF DISTRIBUTION OF ALBIGLUTIDE FOLLOWING SC ADMINISTRATION IS 11 L. AS ALBIGLUTIDE IS AN ALBUMIN FUSION MOLECULE, PLASMA PROTEIN BINDING HAS NOT BEEN ASSESSED.
METABOLISM
ALBIGLUTIDE IS A PROTEIN FOR WHICH THE EXPECTED METABOLIC PATHWAY IS DEGRADATION TO SMALL PEPTIDES AND INDIVIDUAL AMINO ACIDS BY UBIQUITOUS PROTEOLYTIC ENZYMES. CLASSICAL BIOTRANSFORMATION STUDIES HAVE NOT BEEN PERFORMED. BECAUSE ALBIGLUTIDE IS AN ALBUMIN FUSION PROTEIN, IT LIKELY FOLLOWS A METABOLIC PATHWAY SIMILAR TO NATIVE HUMAN SERUM ALBUMIN WHICH IS CATABOLIZED PRIMARILY IN THE VASCULAR ENDOTHELIUM.
ELIMINATION
THE MEAN APPARENT CLEARANCE OF ALBIGLUTIDE IS 67 ML/H WITH AN ELIMINATION HALF-LIFE OF APPROXIMATELY 5 DAYS, MAKING ALBIGLUTIDE SUITABLE FOR ONCE-WEEKLY ADMINISTRATION.
SPECIFIC PATIENT POPULATIONS
AGE, GENDER, RACE, AND BODY WEIGHT: BASED ON THE POPULATION PHARMACOKINETIC ANALYSIS WITH DATA COLLECTED FROM 1,113 SUBJECTS, AGE, GENDER, RACE, AND BODY WEIGHT HAD NO CLINICALLY RELEVANT EFFECT ON THE PHARMACOKINETICS OF ALBIGLUTIDE.
PEDIATRIC: NO PHARMACOKINETIC DATA ARE AVAILABLE IN PEDIATRIC PATIENTS.
RENAL: IN A POPULATION PHARMACOKINETIC ANALYSIS INCLUDING A PHASE III TRIAL IN PATIENTS WITH MILD, MODERATE, AND SEVERE RENAL IMPAIRMENT, EXPOSURES WERE INCREASED BY APPROXIMATELY 30% TO 40% IN SEVERE RENAL IMPAIRMENT COMPARED WITH THOSE OBSERVED IN TYPE 2 DIABETIC PATIENTS WITH NORMAL RENAL FUNCTION.
HEPATIC: NO CLINICAL TRIALS WERE CONDUCTED TO EXAMINE THE EFFECTS OF MILD, MODERATE, OR SEVERE HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS OF ALBIGLUTIDE. THERAPEUTIC PROTEINS SUCH AS ALBIGLUTIDE ARE CATABOLIZED BY WIDELY DISTRIBUTED PROTEOLYTIC ENZYMES, WHICH ARE NOT RESTRICTED TO HEPATIC TISSUE; THEREFORE, CHANGES IN HEPATIC FUNCTION ARE UNLIKELY TO HAVE ANY EFFECT ON THE ELIMINATION OF ALBIGLUTIDE.
DRUG INTERACTIONS
IN MULTIPLE-DOSE, DRUG-DRUG INTERACTION TRIALS NO SIGNIFICANT CHANGE IN SYSTEMIC EXPOSURES OF THE CO-ADMINISTERED DRUGS WERE OBSERVED, EXCEPT SIMVASTATIN (SEE TABLE 3). WHEN ALBIGLUTIDE WAS CO-ADMINISTERED WITH SIMVASTATIN, CMAX OF SIMVASTATIN AND ITS ACTIVE METABOLITE SIMVASTATIN ACID WAS INCREASED BY APPROXIMATELY 18% AND 98%, RESPECTIVELY. IN THE SAME TRIAL, AUC OF SIMVASTATIN DECREASED BY 40% AND AUC OF SIMVASTATIN ACID INCREASED BY 36%. CLINICAL RELEVANCE OF THESE CHANGES HAS NOT BEEN ESTABLISHED (SEE TABLE 3).
ADDITIONALLY, NO CLINICALLY RELEVANT PHARMACODYNAMIC EFFECTS ON LUTEINIZING HORMONE, FOLLICLE-STIMULATING HORMONE, OR PROGESTERONE WERE OBSERVED WHEN ALBIGLUTIDE AND A COMBINATION ORAL CONTRACEPTIVE WERE CO-ADMINISTERED. ALBIGLUTIDE DID NOT SIGNIFICANTLY ALTER THE PHARMACODYNAMIC EFFECTS OF WARFARIN AS MEASURED BY THE INTERNATIONAL NORMALIZED RATIO (INR).
TABLE 3: EFFECT OF ALBIGLUTIDE ON SYSTEMIC EXPOSURE OF CO-ADMINISTERED DRUGS
CLINICAL STUDIES
TANZEUM HAS BEEN STUDIED AS MONOTHERAPY AND IN COMBINATION WITH METFORMIN, METFORMIN AND A SULFONYLUREA, A THIAZOLIDINEDIONE (WITH AND WITHOUT METFORMIN), AND INSULIN GLARGINE (WITH OR WITHOUT ORAL ANTI-DIABETIC DRUGS). THE EFFICACY OF TANZEUM WAS COMPARED WITH PLACEBO, GLIMEPIRIDE, PIOGLITAZONE, LIRAGLUTIDE, SITAGLIPTIN, INSULIN LISPRO, AND INSULIN GLARGINE.
TRIALS EVALUATED THE USE OF TANZEUM 30 MG AND 50 MG. FIVE OF THE 8 TRIALS ALLOWED OPTIONAL UPTITRATION OF TANZEUM FROM 30 MG TO 50 MG IF GLYCEMIC RESPONSE WITH 30 MG WAS INADEQUATE.
IN PATIENTS WITH TYPE 2 DIABETES MELLITUS, TANZEUM PRODUCED CLINICALLY RELEVANT REDUCTION FROM BASELINE IN HBA1C COMPARED WITH PLACEBO. NO OVERALL DIFFERENCES IN GLYCEMIC EFFECTIVENESS OR BODY WEIGHT WERE OBSERVED ACROSS DEMOGRAPHIC SUBGROUPS (AGE, GENDER, RACE/ETHNICITY, DURATION OF DIABETES).
MONOTHERAPY
THE EFFICACY OF TANZEUM AS MONOTHERAPY WAS EVALUATED IN A 52-WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER TRIAL. IN THIS TRIAL, 296 PATIENTS WITH TYPE 2 DIABETES INADEQUATELY CONTROLLED ON DIET AND EXERCISE WERE RANDOMIZED (1:1:1) TO TANZEUM 30 MG SC ONCE WEEKLY, TANZEUM 30 MG SC ONCE WEEKLY UPTITRATED TO 50 MG ONCE WEEKLY AT WEEK 12, OR PLACEBO. THE MEAN AGE OF PARTICIPANTS WAS 53 YEARS, 55% OF PATIENTS WERE MEN, THE MEAN DURATION OF DIABETES WAS 4 YEARS, AND THE MEAN BASELINE EGFR WAS 84 ML/MIN/1.73 M². PRIMARY AND SECONDARY EFFICACY RESULTS ARE PRESENTED IN TABLE 4. FIGURE 1 SHOWS THE MEAN ADJUSTED CHANGES IN HBA1C FROM BASELINE ACROSS STUDY VISITS.
COMPARED WITH PLACEBO, TREATMENT WITH TANZEUM 30 MG OR 50 MG RESULTED IN STATISTICALLY SIGNIFICANT REDUCTIONS IN HBA1C FROM BASELINE AT WEEK 52 (SEE TABLE 4). THE ADJUSTED MEAN CHANGE IN WEIGHT FROM BASELINE DID NOT DIFFER SIGNIFICANTLY BETWEEN TANZEUM (-0.4 TO -0.9 KG) AND PLACEBO (-0.7 KG) AT WEEK 52.
TABLE 4: RESULTS ATWEEK 52 (LOCFA) IN A TRIAL OF TANZEUM AS MONOTHERAPY
PLACEBO TANZEUM 30 MG WEEKLY TANZEUM 50 MG WEEKLY
ITTA (N) 99 100 97
HBA1C (%)
BASELINE (MEAN) 8.0 8.1 8.2
CHANGE AT WEEK 52B +0.2 -0.7 -0.9
DIFFERENCE FROM PLACEBOB (95% CI) -0.8
(-1.1, -0.6)C -1.0
(-1.3, -0.8)C
PATIENTS (%) ACHIEVING HBA1C < 7% 21 49 40
FPG (MG/DL)
BASELINE (MEAN) 163 164 171
CHANGE AT WEEK 52B +18 -16 -25
DIFFERENCE FROM PLACEBOB (95% CI) -34
(-46, -22)C -43
(-55, -31)C
A INTENT-TO-TREAT POPULATION. LAST OBSERVATION CARRIED FORWARD (LOCF) WAS USED TO IMPUTE MISSING DATA. DATA POST-ONSET OF RESCUE THERAPY ARE TREATED AS MISSING. AT WEEK 52, PRIMARY EFFICACY DATA WAS IMPUTED FOR 63%, 34%, AND 41% OF INDIVIDUALS RANDOMIZED TO PLACEBO, TANZEUM 30 MG, AND TANZEUM 50 MG.
B LEAST SQUARES MEAN ADJUSTED FOR BASELINE VALUE AND STRATIFICATION FACTORS.
C P < 0.0001 FOR TREATMENT DIFFERENCE.
FIGURE 1: MEAN HBA1C CHANGE FROM BASELINE (ITT POPULATION-LOCF) IN A TRIAL OF TANZEUM AS MONOTHERAPY
COMBINATION THERAPY
ADD-ON TO METFORMIN
THE EFFICACY OF TANZEUM WAS EVALUATED IN A 104-WEEK RANDOMIZED, DOUBLE-BLIND, MULTICENTER TRIAL IN 999 PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON BACKGROUND METFORMIN THERAPY ( ? 1,500 MG DAILY). IN THIS TRIAL, TANZEUM 30 MG SC WEEKLY (WITH OPTIONAL UPTITRATION TO 50 MG WEEKLY AFTER A MINIMUM OF 4 WEEKS) WAS COMPARED WITH PLACEBO, SITAGLIPTIN 100 MG DAILY, OR GLIMEPIRIDE 2 MG DAILY (WITH OPTIONAL TITRATION TO 4 MG DAILY). THE MEAN AGE OF PARTICIPANTS WAS 55 YEARS, 48% OF PATIENTS WERE MEN, THE MEAN DURATION OF TYPE 2 DIABETES WAS 6 YEARS, AND THE MEAN BASELINE EGFR WAS 86 ML/MIN/1.73 M². RESULTS OF THE PRIMARY AND SECONDARY ANALYSES ARE PRESENTED IN TABLE 5. FIGURE 2 SHOWS THE MEAN ADJUSTED CHANGES IN HBA1C ACROSS STUDY VISITS.
REDUCTION IN HBA1C FROM BASELINE ACHIEVED WITH TANZEUM WAS SIGNIFICANTLY GREATER THAN HBA1C REDUCTION ACHIEVED WITH PLACEBO, SITAGLIPTIN, AND GLIMEPIRIDE AT WEEK 104 (SEE TABLE 5). THE DIFFERENCE IN BODY WEIGHT CHANGE FROM BASELINE BETWEEN TANZEUM AND GLIMEPIRIDE WAS SIGNIFICANT AT WEEK 104.
TABLE 5: RESULTS AT WEEK 104 (LOCFA) IN A TRIAL COMPARING TANZEUM WITH PLACEBO AS ADD-ON THERAPY IN PATIENTS INADEQUATELY CONTROLLED ON METFORMIN
TANZEUM +METFORMIN PLACEBO+ METFORMIN SITAGLIPTIN+ METFORMIN GLIMEPIRIDE+ METFORMIN
ITTA (N) 297 100 300 302
HBA1C (%)
BASELINE (MEAN) 8.1 8.1 8.1 8.1
CHANGE AT WEEK 104B -0.6 +0.3 -0.3 -0.4
DIFFERENCE FROM PLACEBO + METFORMINB (95% CI) -0.9
(-1.16, -0.65)C
DIFFERENCE FROM SITAGLIPTIN + METFORMINB (95% CI) -0.4
(-0.53, -0.17)C
DIFFERENCE FROM GLIMEPIRIDE + METFORMINB (95% CI) -0.3
(-0.45, -0.09)C
PROPORTION ACHIEVING HBA1C < 7% 39 16 32 31
FPG (MG/DL)
BASELINE (MEAN) 165 162 165 168
CHANGE AT WEEK 104B -18 +10 -2 -8
DIFFERENCE FROM PLACEBO + METFORMINB (95% CI) -28
(-39, -16)C
DIFFERENCE FROM SITAGLIPTIN + METFORMINB (95% CI) -16
(-24, -8)C
DIFFERENCE FROM GLIMEPIRIDE + METFORMINB (95% CI) -10
(-18, -2)C
BODY WEIGHT (KG)
BASELINE (MEAN) 90 92 90 92
CHANGE AT WEEK 104 B -1.2 -1.0 -0.9 +1.2
DIFFERENCE FROM PLACEBO + METFORMINB (95% CI) -0.2
(-1.1, 0.7)
DIFFERENCE FROM SITAGLIPTIN + METFORMINB (95% CI) -0.4
(-1.0, 0.3)
DIFFERENCE FROM GLIMEPIRIDE + METFORMINB (95% CI) -2.4 (-3.0, -1.7)C
A INTENT-TO-TREAT POPULATION. LAST OBSERVATION CARRIED FORWARD (LOCF) WAS USED TO IMPUTE MISSING DATA. DATA POST-ONSET OF RESCUE THERAPY ARE TREATED AS MISSING. AT WEEK 104, PRIMARY EFFICACY DATA WAS IMPUTED FOR 76%, 46%, 55%, AND 51% OF INDIVIDUALS RANDOMIZED TO PLACEBO, TANZEUM, SITAGLIPTIN, AND GLIMEPIRIDE, RESPECTIVELY.
B LEAST SQUARES MEAN ADJUSTED FOR BASELINE VALUE AND STRATIFICATION FACTORS.
C P < 0.0137 FOR TREATMENT DIFFERENCE.
FIGURE 2: MEAN HBA1C OVER TIME (ITT POPULATION-LOCF) IN A TRIAL COMPARING TANZEUM WITH PLACEBO AS ADD-ON THERAPY IN PATIENTS INADEQUATELY CONTROLLED ON METFORMIN
ADD-ON TO PIOGLITAZONE
THE EFFICACY OF TANZEUM WAS EVALUATED IN A 52-WEEK RANDOMIZED, DOUBLE-BLIND, MULTICENTER TRIAL IN 299 PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON PIOGLITAZONE ? 30 MG DAILY (WITH OR WITHOUT METFORMIN ? 1,500 MG DAILY). PATIENTS WERE RANDOMIZED TO RECEIVE TANZEUM 30 MG SC WEEKLY OR PLACEBO. THE MEAN AGE OF PARTICIPANTS WAS 55 YEARS, 60% OF PATIENTS WERE MEN, THE MEAN DURATION OF TYPE 2 DIABETES WAS 8 YEARS, AND THE MEAN BASELINE EGFR WAS 83 ML/MIN/1.73 M². RESULTS OF THE PRIMARY AND SECONDARY ANALYSES ARE PRESENTED IN TABLE 6.
COMPARED WITH PLACEBO, TREATMENT WITH TANZEUM RESULTED IN A STATISTICALLY SIGNIFICANT REDUCTION IN HBA1C FROM BASELINE AT WEEK 52 (SEE TABLE 6). THE ADJUSTED MEAN CHANGE FROM BASELINE IN WEIGHT DID NOT DIFFER SIGNIFICANTLY BETWEEN TANZEUM (+0.3 KG) AND PLACEBO (+0.5 KG) AT WEEK 52.
TABLE 6: RESULTS AT WEEK 52 (LOCFA) IN A TRIAL COMPARING TANZEUM WITH PLACEBO AS ADD-ON THERAPY IN PATIENTS INADEQUATELY CONTROLLED ON PIOGLITAZONE (WITH OR WITHOUT METFORMIN)
TANZEUM + PIOGLITAZONE (WITH OR WITHOUT METFORMIN) PLACEBO + PIOGLITAZONE (WITH OR WITHOUT METFORMIN)
ITTA (N) 150 149
HBA1C (%)
BASELINE (MEAN) 8.1 8.1
CHANGE AT WEEK 52B -0.8 -0.1
DIFFERENCE FROM PLACEBO + PIOGLITAZONEB (95% CI) -0.8 (-0.95, -0.56)C
PROPORTION ACHIEVING HBA1C < 7% 44 15
FPG (MG/DL)
BASELINE (MEAN) 165 167
CHANGE AT WEEK 52B -23 +6
DIFFERENCE FROM PLACEBO + PIOGLITAZONEB (95% CI) -30 (-39, -20)C
A INTENT-TO-TREAT POPULATION. LAST OBSERVATION CARRIED FORWARD (LOCF) WAS USED TO IMPUTE MISSING DATA. DATA POST-ONSET OF RESCUE THERAPY ARE TREATED AS MISSING. AT WEEK 52, PRIMARY EFFICACY DATA WAS IMPUTED FOR 58% AND 32% OF INDIVIDUALS RANDOMIZED TO PLACEBO AND TANZEUM, RESPECTIVELY.
B LEAST SQUARES MEAN ADJUSTED FOR BASELINE VALUE AND STRATIFICATION FACTORS.
C P < 0.0001 FOR TREATMENT DIFFERENCE.
ADD-ON TO METFORMIN PLUS SULFONYLUREA
THE EFFICACY OF TANZEUM WAS EVALUATED IN A 52-WEEK RANDOMIZED, DOUBLE-BLIND, MULTICENTER TRIAL IN 657 PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON METFORMIN ( ? 1,500 MG DAILY) AND GLIMEPIRIDE (4 MG DAILY). PATIENTS WERE RANDOMIZED TO RECEIVE TANZEUM 30 MG SC WEEKLY (WITH OPTIONAL UPTITRATION TO 50 MG WEEKLY AFTER A MINIMUM OF 4 WEEKS), PLACEBO, OR PIOGLITAZONE 30 MG DAILY (WITH OPTIONAL TITRATION TO 45 MG/DAY). THE MEAN AGE OF PARTICIPANTS WAS 55 YEARS, 53% OF PATIENTS WERE MEN, THE MEAN DURATION OF TYPE 2 DIABETES WAS 9 YEARS, AND THE MEAN BASELINE EGFR WAS 84 ML/MIN/1.73 M². RESULTS OF THE PRIMARY AND MAIN SECONDARY ANALYSES ARE PRESENTED IN TABLE 7.
TREATMENT WITH TANZEUM RESULTED IN STATISTICALLY SIGNIFICANT REDUCTIONS IN HBA1C FROM BASELINE COMPARED WITH PLACEBO (SEE TABLE 7). TREATMENT WITH TANZEUM DID NOT MEET THE PRE-SPECIFIED, NON-INFERIORITY MARGIN (0.3%) AGAINST PIOGLITAZONE. IN THIS TRIAL, TANZEUM PROVIDED LESS HBA1C REDUCTION THAN PIOGLITAZONE AND THE TREATMENT DIFFERENCE WAS STATISTICALLY SIGNIFICANT (SEE TABLE 7). THE CHANGE FROM BASELINE IN BODY WEIGHT FOR TANZEUM DID NOT DIFFER SIGNIFICANTLY FROM PLACEBO BUT WAS SIGNIFICANTLY DIFFERENT COMPARED WITH PIOGLITAZONE (SEE TABLE 7).
TABLE 7: RESULTS AT WEEK 52 (LOCFA) IN A TRIAL COMPARING TANZEUM WITH PLACEBO AS ADD-ON THERAPY IN PATIENTS INADEQUATELY CONTROLLED ON METFORMIN PLUS SULFONYLUREA
TANZEUM + METFORMIN + GLIMEPIRIDE PLACEBO + METFORMIN + GLIMEPIRIDE PIOGLITAZONE + METFORMIN + GLIMEPIRIDE
ITTA (N) 269 115 273
HBA1C (%)
BASELINE (MEAN) 8.2 8.3 8.3
CHANGE AT WEEK 52B -0.6 +0.3 -0.8
DIFFERENCE FROM PLACEBO + MET + GLIMB (95% CI) -0.9 (-1.07, -0.68)C
DIFFERENCE FROM PIOGLITAZONE + MET + GLIMB (95% CI) 0.25 (0.10, 0.40)D
PROPORTION ACHIEVING HBA1C < 7% 30 9 35
FPG (MG/DL)
BASELINE (MEAN) 171 174 177
CHANGE AT WEEK 52B -12 +12 -31
DIFFERENCE FROM PLACEBO + MET + GLIMB (95% CI) -24 (-34, -14)C
DIFFERENCE FROM PIOGLITAZONE + MET + GLIMB (95% CI) 19 (11, 27)C
BODY WEIGHT (KG)
BASELINE (MEAN) 91 90 91
CHANGE AT WEEK 52B -0.4 -0.4 +4.4
DIFFERENCE FROM PLACEBO + MET + GLIMB (95% CI) -0.0 (-0.9, 0.8)
DIFFERENCE FROM PIOGLITAZONE + MET + GLIMB (95% CI) -4.9 (-5.5, -4.2)C
A INTENT-TO-TREAT POPULATION. LAST OBSERVATION CARRIED FORWARD (LOCF) WAS USED TO IMPUTE MISSING DATA. DATA POST-ONSET OF RESCUE THERAPY ARE TREATED AS MISSING. AT WEEK 52, PRIMARY EFFICACY DATA WAS IMPUTED FOR 70%, 35%, AND 34% OF INDIVIDUALS RANDOMIZED TO PLACEBO, TANZEUM, AND PIOGLITAZONE.
B LEAST SQUARES MEAN ADJUSTED FOR BASELINE VALUE AND STRATIFICATION FACTORS.
C P < 0.0001 FOR TREATMENT DIFFERENCE.
D DID NOT MEET NON-INFERIORITY MARGIN OF 0.3%.
COMBINATION THERAPY: ACTIVE-CONTROLLED TRIAL VERSUS LIRAGLUTIDE
THE EFFICACY OF TANZEUM WAS EVALUATED IN A 32-WEEK, RANDOMIZED, OPEN-LABEL, LIRAGLUTIDE-CONTROLLED, NON-INFERIORITY TRIAL IN 805 PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON MONOTHERAPY OR COMBINATION ORAL ANTIDIABETIC THERAPY (METFORMIN, THIAZOLIDINEDIONE, SULFONYLUREA, OR A COMBINATION OF THESE). PATIENTS WERE RANDOMIZED TO TANZEUM 30 MG SC WEEKLY (WITH UPTITRATION TO 50 MG WEEKLY AT WEEK 6) OR LIRAGLUTIDE 1.8 MG DAILY (TITRATED UP FROM 0.6 MG AT WEEK 1, AND 1.2 MG AT WEEK 1 TO WEEK 2). THE MEAN AGE OF PARTICIPANTS WAS 56 YEARS, 50% OF PATIENTS WERE MEN, THE MEAN DURATION OF TYPE 2 DIABETES WAS 8 YEARS, AND THE MEAN BASELINE EGFR WAS 95 ML/MIN/1.73 M². RESULTS OF THE PRIMARY AND MAIN SECONDARY ANALYSES ARE PRESENTED IN TABLE 8.
THE BETWEEN-TREATMENT DIFFERENCE OF 0.2% WITH 95% CONFIDENCE INTERVAL (0.08, 0.34) BETWEEN TANZEUM AND LIRAGLUTIDE DID NOT MEET THE PRE-SPECIFIED, NON-INFERIORITY MARGIN (0.3%). IN THIS TRIAL, TANZEUM PROVIDED LESS HBA1C REDUCTION THAN LIRAGLUTIDE AND THE TREATMENT DIFFERENCE WAS STATISTICALLY SIGNIFICANT (SEE TABLE 8).
TABLE 8: RESULTS OF CONTROLLED TRIAL OF TANZEUM VERSUS LIRAGLUTIDE AT WEEK 32 (LOCFA)
TANZEUM LIRAGLUTIDE
ITTA (N) 402 403
HBA1C (%)
BASELINE (MEAN) 8.2% 8.2%
CHANGE AT WEEK 32B -0.8 -1.0
DIFFERENCE FROM LIRAGLUTIDEB (95% CI) 0.2 (0.08, 0.34)C
PROPORTION ACHIEVING HBA1C < 7% 42% 52%
FPG (MG/DL)
BASELINE (MEAN) 169 167
CHANGE AT WEEK 32B -22 -30
DIFFERENCE FROM LIRAGLUTIDEB (95% CI) 8 (3, 14)D
BODY WEIGHT (KG)
BASELINE (MEAN) 92 93
CHANGE AT WEEK 32B -0.6 -2.2
DIFFERENCE FROM LIRAGLUTIDEB (95% CI) 1.6 (1.1, 2.1)D
A INTENT-TO-TREAT POPULATION. LAST OBSERVATION CARRIED FORWARD (LOCF) WAS USED TO IMPUTE MISSING DATA. DATA POST-ONSET OF RESCUE THERAPY ARE TREATED AS MISSING. AT WEEK 32, PRIMARY EFFICACY DATA WAS IMPUTED FOR 31% AND 24% OF INDIVIDUALS RANDOMIZED TO TANZEUM AND LIRAGLUTIDE.
B LEAST SQUARES MEAN ADJUSTED FOR BASELINE VALUE AND STRATIFICATION FACTORS.
C DID NOT MEET NON-INFERIORITY MARGIN OF 0.3%.
D P < 0.005 FOR TREATMENT DIFFERENCE IN FAVOR OF LIRAGLUTIDE.
COMBINATION THERAPY: ACTIVE-CONTROLLED TRIAL VERSUS BASAL INSULIN
THE EFFICACY OF TANZEUM WAS EVALUATED IN A 52-WEEK, RANDOMIZED (2:1), OPEN-LABEL, INSULIN GLARGINE-CONTROLLED, NON-INFERIORITY TRIAL IN 735 PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON METFORMIN ? 1,500 MG DAILY (WITH OR WITHOUT SULFONYLUREA). PATIENTS WERE RANDOMIZED TO RECEIVE TANZEUM 30 MG SC WEEKLY (WITH OPTIONAL UPTITRATION TO 50 MG WEEKLY) OR INSULIN GLARGINE (STARTED AT 10 UNITS AND TITRATED WEEKLY PER PRESCRIBING INFORMATION). THE PRIMARY ENDPOINT WAS CHANGE IN HBA1C FROM BASELINE COMPARED WITH INSULIN GLARGINE. THE STARTING TOTAL DAILY DOSE OF INSULIN GLARGINE RANGED BETWEEN 2 AND 40 UNITS (MEDIAN DAILY DOSE OF 10 UNITS) AND RANGED BETWEEN 3 AND 230 UNITS (MEDIAN DAILY DOSE OF 30 UNITS) AT WEEK 52. SEVENTY-SEVEN PERCENT OF PATIENTS TREATED WITH TANZEUM WERE UPTITRATED TO 50 MG SC WEEKLY. THE MEAN AGE OF PARTICIPANTS WAS 56 YEARS, 56% OF PATIENTS WERE MEN, THE MEAN DURATION OF TYPE 2 DIABETES WAS 9 YEARS, AND THE MEAN BASELINE EGFR WAS 85 ML/MIN/1.73 M². RESULTS OF THE PRIMARY AND MAIN SECONDARY ANALYSES ARE PRESENTED IN TABLE 9.
THE BETWEEN-TREATMENT DIFFERENCE OF 0.1% WITH 95% CONFIDENCE INTERVAL (-0.04%, 0.27%) FOR TANZEUM AND INSULIN GLARGINE MET THE PRE-SPECIFIED, NON-INFERIORITY MARGIN (0.3%). A MEAN DECREASE IN BODY WEIGHT WAS OBSERVED FOR TANZEUM COMPARED WITH A MEAN INCREASE IN BODY WEIGHT FOR INSULIN GLARGINE, AND THE DIFFERENCE IN WEIGHT CHANGE WAS STATISTICALLY SIGNIFICANT (SEE TABLE 9).
TABLE 9: RESULTS AT WEEK 52 (LOCFA) IN A TRIAL COMPARING TANZEUM WITH INSULIN GLARGINE AS ADD-ON THERAPY IN PATIENTS INADEQUATELY CONTROLLED ON METFORMIN ± SULFONYLUREA
TANZEUM + METFORMIN (WITH OR WITHOUT SULFONYLUREA) INSULIN GLARGINE + METFORMIN (WITH OR WITHOUT SULFONYLUREA)
ITTA (N) 496 239
HBA1C (%)
BASELINE (MEAN) 8.3 8.4
CHANGE AT WEEK 52B -0.7 -0.8
DIFFERENCE FROM INSULIN GLARGINEB (95% CI) 0.1 (-0.04, 0.27)C
PROPORTION ACHIEVING HBA1C < 7% 32 33
FPG (MG/DL)
BASELINE (MEAN) 169 175
CHANGE AT WEEK 52B -16 -37
DIFFERENCE FROM INSULIN GLARGINEB (95% CI) 21 (14, 29)D
BODY WEIGHT (KG)
BASELINE (MEAN) 95 95
CHANGE AT WEEK 52B -1.1 1.6
DIFFERENCE FROM INSULIN GLARGINEB (95% CI) -2.6 (-3.2, -2.0)E
A INTENT-TO-TREAT POPULATION. LAST OBSERVATION CARRIED FORWARD (LOCF) WAS USED TO IMPUTE MISSING DATA. DATA POST-ONSET OF RESCUE THERAPY ARE TREATED AS MISSING. AT WEEK 52, PRIMARY EFFICACY DATA WAS IMPUTED FOR 41% AND 36% OF INDIVIDUALS RANDOMIZED TO TANZEUM AND INSULIN GLARGINE.
B LEAST SQUARES MEAN ADJUSTED FOR BASELINE VALUE AND STRATIFICATION FACTORS.
C MET NON-INFERIORITY MARGIN OF 0.3%.
D P < 0.0001 IN FAVOR OF INSULIN GLARGINE.
E P < 0.0001.
FIGURE 3: MEAN HBA1C CHANGE FROM BASELINE (COMPLETERS) IN A TRIAL COMPARING TANZEUM WITH INSULIN GLARGINE AS ADD-ON THERAPY IN PATIENTS INADEQUATELY CONTROLLED ON METFORMIN (WITH OR WITHOUT A SULFONYLUREA)
COMBINATION THERAPY: ACTIVE-CONTROLLED TRIAL VERSUS PRANDIAL INSULIN
THE EFFICACY OF TANZEUM WAS EVALUATED IN A 26-WEEK, RANDOMIZED, OPEN-LABEL, MULTICENTER, NON-INFERIORITY TRIAL IN 563 PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON INSULIN GLARGINE (STARTED AT 10 UNITS AND TITRATED TO ? 20 UNITS PER DAY). PATIENTS WERE RANDOMIZED TO RECEIVE TANZEUM 30 MG SC ONCE WEEKLY (WITH UPTITRATION TO 50 MG IF INADEQUATELY CONTROLLED AFTER WEEK 8) OR INSULIN LISPRO (ADMINISTERED DAILY AT MEAL TIMES, STARTED ACCORDING TO STANDARD OF CARE AND TITRATED TO EFFECT). AT WEEK 26, THE MEAN DAILY DOSE OF INSULIN GLARGINE WAS 53 IU FOR TANZEUM AND 51 IU FOR INSULIN LISPRO. THE MEAN DAILY DOSE OF INSULIN LISPRO AT WEEK 26 WAS 31 IU, AND 69% OF PATIENTS TREATED WITH TANZEUM WERE ON 50 MG WEEKLY. THE MEAN AGE OF PARTICIPANTS WAS 56 YEARS, 47% OF PATIENTS WERE MEN, THE MEAN DURATION OF TYPE 2 DIABETES WAS 11 YEARS, AND THE MEAN BASELINE EGFR WAS 91 ML/MIN/1.73 M². RESULTS OF THE PRIMARY AND MAIN SECONDARY ANALYSES ARE PRESENTED IN TABLE 10. FIGURE 4 SHOWS THE MEAN ADJUSTED CHANGES IN HBA1C FROM BASELINE ACROSS STUDY VISITS.
THE BETWEEN-TREATMENT DIFFERENCE OF -0.2% WITH 95% CONFIDENCE INTERVAL (-0.32%, 0.00%) BETWEEN ALBIGLUTIDE AND INSULIN LISPRO MET THE PRE-SPECIFIED NON-INFERIORITY MARGIN (0.4%). TREATMENT WITH TANZEUM RESULTED IN A MEAN WEIGHT LOSS FOR TANZEUM COMPARED WITH A MEAN WEIGHT GAIN FOR INSULIN LISPRO, AND THE DIFFERENCE BETWEEN TREATMENT GROUPS WAS STATISTICALLY SIGNIFICANT (SEE TABLE 10).
TABLE 10: RESULTS AT WEEK 26 (LOCFA) IN A TRIAL COMPARING TANZEUM WITH INSULIN LISPRO AS ADD-ON THERAPY IN PATIENTS INADEQUATELY CONTROLLED ON INSULIN GLARGINE
TANZEUM + INSULIN GLARGINE INSULIN LISPRO + INSULIN GLARGINE
ITTA (N) 282 281
HBA1C (%)
BASELINE (MEAN) 8.5 8.4
CHANGE AT WEEK 26B -0.8 -0.7
DIFFERENCE FROM INSULIN LISPROB (95% CI) -0.2 (-0.32, 0.00)C
PROPORTION ACHIEVING HBA1C < 7% 30% 25%
FPG (MG/DL)
BASELINE (MEAN) 153 153
CHANGE AT WEEK 26B -18 -13
DIFFERENCE FROM INSULIN LISPROB (95% CI) -5 (-13, 3)
BODY WEIGHT (KG)
BASELINE (MEAN) 93 92
CHANGE AT WEEK 26B -0.7 +0.8
DIFFERENCE FROM INSULIN LISPROB (95% CI) -1.5 (-2.1, -1.0)D
A INTENT-TO-TREAT POPULATION. LAST OBSERVATION CARRIED FORWARD (LOCF) WAS USED TO IMPUTE MISSING DATA. DATA POST-ONSET OF RESCUE THERAPY ARE TREATED AS MISSING. AT WEEK 26, PRIMARY EFFICACY DATA WAS IMPUTED FOR 29% AND 29% OF INDIVIDUALS RANDOMIZED TO TANZEUM AND INSULIN LISPRO.
B LEAST SQUARES MEAN ADJUSTED FOR BASELINE VALUE AND STRATIFICATION FACTORS.
C RULES OUT A NON-INFERIORITY MARGIN OF 0.4%.
D P < 0.0001 FOR TREATMENT DIFFERENCE.
FIGURE 4: MEAN HBA1C CHANGE FROM BASELINE (ITT-LOCF POPULATION) IN A TRIAL COMPARING TANZEUM WITH INSULIN LISPRO AS ADD-ON THERAPY IN PATIENTS INADEQUATELY CONTROLLED ON INSULIN GLARGINE
TYPE 2 DIABETES MELLITUS PATIENTS WITH RENAL IMPAIRMENT
THE EFFICACY OF TANZEUM WAS EVALUATED IN A 26-WEEK, RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED TRIAL IN 486 PATIENTS WITH MILD (N = 250), MODERATE (N = 200), AND SEVERE RENAL IMPAIRMENT (N = 36) INADEQUATELY CONTROLLED ON A CURRENT REGIMEN OF DIET AND EXERCISE OR OTHER ANTIDIABETIC THERAPY. PATIENTS WERE RANDOMIZED TO RECEIVE TANZEUM 30 MG SC WEEKLY (WITH UPTITRATION TO 50 MG WEEKLY IF NEEDED AS EARLY AS WEEK 4) OR SITAGLIPTIN. SITAGLIPTIN WAS DOSED ACCORDING TO RENAL FUNCTION (100 MG, 50 MG, AND 25 MG DAILY IN MILD, MODERATE, AND SEVERE RENAL IMPAIRMENT, RESPECTIVELY). THE MEAN AGE OF PARTICIPANTS WAS 63 YEARS, 54% OF PATIENTS WERE MEN, THE MEAN DURATION OF TYPE 2 DIABETES WAS 11 YEARS, AND THE MEAN BASELINE EGFR WAS 60 ML/MIN/1.73 M².
RESULTS OF THE PRIMARY AND MAIN SECONDARY ANALYSES ARE PRESENTED IN TABLE 11. TREATMENT WITH TANZEUM RESULTED IN STATISTICALLY SIGNIFICANT REDUCTIONS IN HBA1C FROM BASELINE AT WEEK 26 COMPARED WITH SITAGLIPTIN (SEE TABLE 11).
TABLE 11: RESULTS AT WEEK 26 (LOCFA) IN A TRIAL COMPARING TANZEUM WITH SITAGLIPTIN IN PATIENTS WITH RENAL IMPAIRMENT
TANZEUM SITAGLIPTIN
ITTA (N) 246 240
HBA1C (%)
BASELINE (MEAN) 8.1 8.2
CHANGE AT WEEK 26B -0.8 -0.5
DIFFERENCE FROM SITAGLIPTINB (95% CI) -0.3 (-0.49, -0.15)C
PROPORTION ACHIEVING HBA1C < 7% 43% 31%
FPG (MG/DL)
BASELINE (MEAN) 166 165
CHANGE AT WEEK 26B -26 -4
DIFFERENCE FROM SITAGLIPTINB (95% CI) -22 (-31, -13)C
BODY WEIGHT (KG)
BASELINE (MEAN) 84 83
CHANGE AT WEEK 26B -0.8 -0.2
DIFFERENCE FROM SITAGLIPTINB (95% CI) -0.6 (-1.1, -0.1)D
A INTENT-TO-TREAT POPULATION. LAST OBSERVATION CARRIED FORWARD (LOCF) WAS USED TO IMPUTE MISSING DATA. DATA POST-ONSET OF RESCUE THERAPY ARE TREATED AS MISSING. AT WEEK 26 PRIMARY EFFICACY DATA WAS IMPUTED FOR 17% AND 25% OF INDIVIDUALS RANDOMIZED TO TANZEUM AND SITAGLIPTIN.
B LEAST SQUARES MEAN ADJUSTED FOR BASELINE VALUE AND STRATIFICATION FACTORS.
C P < 0.0003 FOR TREATMENT DIFFERENCE.
D P = 0.0281 FOR TREATMENT DIFFERENCE.