Journal name: Lancet

Publishing date: July 10, 2021

Author: Julio Rosenstock et.al

Tirzepatide, a novel dual GIP and GLP-1 analogue is found to be effective in improving glycemic control and body weight in type 2 diabetes mellitus inadequately controlled with diet and exercise alone.

Why does this study matter?

Diabetes is a disease with a huge global burden. A large number of patients have uncontrolled diabetes even after using various treatment options. This study assesses the efficacy and safety of the novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes mellitus (DM) inadequately controlled with diet and exercise alone. 

Study Design

 A 40-week, double-blind, randomised, placebo-controlled, phase 3 trial (SURPASS-1), was conducted at 52 medical research centres and hospitals across India, Japan, Mexico, and the USA which included adult (>/=18 years) participants with type 2 DM inadequately controlled with diet and exercise alone and with no prior injectable antidiabetic treatment.

Computer-generated random sequence was used to assign participants to once a week tirzepatide (5, 10, 15 mg) or placebo and the participants, investigators and sponsors were masked to treatment assignment. Mean change in HbA1C from baseline at 40 weeks was the primary endpoint.

Results and Conclusion

At 40 weeks, all tirzepatide doses were found to be superior to placebo for changes from baseline in HbA1c, fasting serum glucose, body weight, and HbA1c targets of less than 7·0% (<53 mmol/mol) and less than 5·7% (<39 mmol/mol).

1. Mean HbA1c showed reduction from baseline by 1·87% (20 mmol/mol) with tirzepatide 5 mg, 1·89% (21 mmol/mol) with tirzepatide 10 mg, and 2·07% (23 mmol/mol) with tirzepatide 15 mg versus +0·04% with placebo (+0·4 mmol/mol). 
2. Estimated treatment differences for tirzepatide versus placebo were −1·91% (−21 mmol/mol) with tirzepatide 5 mg, −1·93% (−21 mmol/mol) with tirzepatide 10 mg, and −2·11% (−23 mmol/mol) with tirzepatide 15 mg (all p<0·0001).
3. 87-92% of participants on tirzepatide met HbA1c targets of less than 7·0% (<53 mmol/mol) compared to 20% of participants on placebo.
4. 81-86% of participants on tirzepatide met HbA1c targets of 6·5% or less than (≤48 mmol/mol) compared to 10% of participants on placebo.
5. 31-52% of participants on tirzepatide met HbA1c targets of 6·5% or less than 5·7% (<39 mmol/mol) compared to 1% of participants on placebo.
6. Dose-dependent bodyweight loss ranging from 7·0 to 9·5 kg was observed among participants on tirzepatide.

Mild to moderate transient gastrointestinal side effects were reported with tirzepatide and no serious hypoglycemia was reported.

Tirzepatide showed sound improvements in glycemic control and bodyweight reduction without elevated hypoglycemia risk. It can be considered a monotherapy in type 2 DM treatment as the safety profile is comparable to that of GLP-1 analogs.

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