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TIRZEPATIDE (MOUNJARO®)














  • Patients were inadequately controlled on diet and exercise
  • Reference [1]
Effects of Tirzepatide on T2DM in a 40-week Trial
Outcome Placebo
(N=113)		 Tirzepatide 5 mg
(N=121)		 Tirzepatide 10 mg
(N=121)		 Tirzepatide 15 mg
(N=120)
Baseline A1C 8.1% 8.0% 7.9% 7.9%
Change in A1C -0.1% -1.8% -1.7% -1.7
Change in FBS
(mg/dl)		 +4 -40 -40 -39
Baseline weight 186 lbs (84.5 kg) 191 lbs (87 kg) 190 lbs (86.2 kg) 188 lbs (85.5 kg)
Change in weight -2.2 lbs (1 kg) -13.9 lbs (6.3 kg) -15.4 lbs (7 kg) -17.2 lbs (7.8 kg)

SURPASS-2 trial - Tirzepatide vs Semaglutide in Patients with Type 2 Diabetes, NEJM (2021) [PubMed abstract]
  • The SURPASS-2 trial enrolled 1879 adults with type 2 diabetes who were inadequately controlled with metformin at a dose of at least 1500 mg per day
Main inclusion criteria
  • Age ≥ 18 years
  • T2DM uncontrolled with metformin at ≥ 1500 mg/day
  • A1C of 7 - 10.5%
  • BMI ≥ 25 and stable for 3 months
Main exclusion criteria
  • Type 1 diabetes
  • GFR < 45 ml/min
  • History of pancreatitis
  • Significant diabetic retinopathy
Baseline characteristics
  • Average age 57 years
  • Average A1C - 8.28%
  • Average FBS - 173 mg/dl
  • Average BMI - 34
  • Average weight - 206 lbs (93.7 kg)
  • Average length of diabetes - 8.6 years
Randomized treatment groups
  • Group 1 (470 patients): Tirzepatide 5 mg once weekly
  • Group 2 (469 patients): Tirzepatide 10 mg once weekly
  • Group 3 (470 patients): Tirzepatide 15 mg once weekly
  • Group 4 (469 patients): Semaglutide 1 mg once weekly
  • Semaglutide and tirzepatide assignment was open-label. Tirzepatide dosing was double-blind.
  • Tirzepatide was initiated at a dose of 2.5 mg once weekly, and the doses were increased by 2.5 mg every 4 weeks until the randomly assigned dose was reached
  • Semaglutide was initiated at a dose of 0.25 mg once weekly, and the dose was doubled every 4 weeks until 1 mg was reached
  • Metformin was continued. The initiation of new antihyperglycemic medications was allowed according to specific criteria
Primary outcome: Change in the glycated hemoglobin level from baseline to 40 weeks
Results

Duration: 40 weeks
Outcome Tir 5 mg Tir 10 mg Tir 15 mg Sem 1 mg Comparisons
Primary outcome −2.01% −2.24% −2.30% −1.86% Tir (all doses) vs Sem p<0.05
A1C < 7% 82% 86% 86% 79% Tir (10 and 15 mg) vs Sem p<0.05
Weight loss 16.7 lbs (7.6 kg) 20.5 lbs (9.3 kg) 24.6 lbs (11.2 kg) 12.5 lbs (5.7 kg) Tir (all doses) vs Sem p<0.001
Nausea 17.4% 19.2% 22.1% 17.9% N/A
Diarrhea 13.2% 16.4% 13.8% 11.5% N/A
Pancreatitis 0 0.4% 0.4% 0.6% N/A
Hypoglycemia (< 54 mg/dl) 0.6% 0.2% 1.7% 0.4% N/A
Cholelithiasis 0.9% 0.9% 0.9% 0.4% N/A
DM retinopathy 0 0.4% 0 0 N/A
  • Rescue therapy for persistent hyperglycemia was warranted for 1.3 to 1.5% of patients who received tirzepatide and 2.8% of those who received semaglutide
  • Most cases of nausea, vomiting, and diarrhea were transient, mild to moderate in severity, and occurred during the dose-escalation period in all groups
  • No clinically relevant changes in mean calcitonin levels were observed, and no cases of medullary thyroid cancer were reported

Findings: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks.




SURMOUNT-1 trial - Tirzepatide vs Placebo for Weight Loss in Obese Patients Without Diabetes, NEJM (2022) [PubMed abstract]
  • The SURMOUNT-1 trial enrolled 2539 adults with a BMI ≥ 30 or a BMI ≥ 27 and at least one weight-related complication
Main inclusion criteria
  • Age ≥ 18 years
  • History of unsuccessful dieting
  • BMI ≥ 30 or ≥ 27 and 1 or more of the following:
    • Hypertension
    • Dyslipidemia
    • OSA
    • CVD
Main exclusion criteria
  • Diabetes
  • Previous bariatric surgery
  • Other weight loss drug within 90 days
Baseline characteristics
  • Average age 45 years
  • Female sex - 68%
  • Average body weight - 231 lbs (105 kg)
  • Average BMI - 38
Randomized treatment groups
  • Group 1 (630 patients): Tirzepatide 5 mg once weekly
  • Group 2 (636 patients): Tirzepatide 10 mg once weekly
  • Group 3 (630 patients): Tirzepatide 15 mg once weekly
  • Group 4 (643 patients): Placebo once weekly
  • Tirzepatide was initiated at a dose of 2.5 mg once weekly (or matching placebo) and was increased by 2.5 mg every 4 weeks during the dose-escalation period to reach a maintenance dose of up to 15 mg once weekly by week 20
Primary outcome: The coprimary end points were the percentage change in body weight from baseline to week 72 and a weight reduction of 5% or more at week 72
Results

Duration: 72 weeks
Outcome Tir 5 mg Tir 10 mg Tir 15 mg Placebo Comparisons
% change in body weight −15% −19.5% −20.9% −3.1% Tir (all doses) vs Placebo p<0.001
≥ 5% weight loss 85% 89% 91% 35% Tir (all doses) vs Placebo p<0.001
Body weight lost 35.5 lbs (16.1 kg) 48.9 lbs (22.2 kg) 52.0 lbs (23.6 kg) 5.3 lb (2.4 kg) N/A
Nausea 24.6% 33.3% 31% 9.5% N/A
Diarrhea 18.7% 21.2% 23% 7.3% N/A
Constipation 16.8% 17.1% 11.7% 5.8% N/A
Pancreatitis 0.2% 0.2% 0.2% 0.2% N/A
Gallbladder disease 0.8% 1.7% 1.0% 0.8% N/A
  • Treatment discontinuations due to adverse events were 4.3%, 7.1%, and 6.2% with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 2.6% with placebo
  • Gastrointestinal side effects were transient, mild to moderate in severity, and occurred primarily during the dose-escalation period

Findings: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight.




  • Reference [1]
Gastrointestinal Side effects
Side effect Placebo
(N=235)		 Tir 5 mg
(N=237)		 Tir 10 mg
(N=240)		 Tir 15 mg
(N=241)
Nausea 4% 12% 15% 18%
Diarrhea 9% 12% 13% 17%
Decreased Appetite 1% 5% 10% 11%
Vomiting 2% 5% 5% 9%
Constipation 1% 6% 6% 7%
Dyspepsia 3% 8% 8% 5%
Abdominal Pain 4% 6% 5% 5%