Tirzepatide Dramatically Lowers Weight and A1C

By Eliza Skoler and Rhea Teng

Full results from the SURPASS trials on the combination drug tirzepatide shows that this new medication dramatically lowers A1C and weight and is incredibly effective in people with type 2 diabetes. Read the latest from four clinical trials.

The eagerly-anticipated, full results of the phase 3 SURPASS trials were shared at ADA 2021. Earlier this year, exciting early results from several trials of tirzepatide showed that the new drug can lead to a sizable A1C reduction, significant weight loss, and less hypoglycemia among people with type 2 diabetes. Tirzepatide is a once-weekly injectable medication. This new glucose-lowering therapy is called a "dual agonist" or a “dual GIP and GLP-1 receptor agonist” and is currently in development to help people manage type 2 diabetes and help provide more stability in terms of weight.

All four clinical trials investigated different doses of tirzepatide (5 mg, 10 mg, and 15) in adults with type 2 diabetes. Two of the trials studied the use of tirzepatide in combination with other treatments, and two of the trials compared tirzepatide to other diabetes drugs:

SURPASS-1 investigated tirzepatide in 478 adults with type 2 diabetes who needed treatment beyond diet and exercise to manage their blood sugar levels. Participants were randomly assigned to a certain dose of tirzepatide or to the placebo group. After 40 weeks, all doses of tirzepatide lowered participants’ A1C, fasting glucose levels, and bodyweight.
SURPASS-2 compared Lilly’s tirzepatide to Novo Nordisk’s GLP-1 agonist semaglutide in 1,879 participants with type 2 diabetes. Participants were randomized to a certain dose of tirzepatide or semaglutide for 40 weeks.
SURPASS-3 compared the effects of tirzepatide to insulin degludec in 1,437 individuals. Participants were randomly assigned to receive a certain dose of tirzepatide or insulin degludec treatment for one year.
SURPASS-5 investigated the safety and efficacy of tirzepatide when combined with basal insulin therapy in 475 people with type 2 diabetes. Participants were randomly assigned to receive a certain dose of tirzepatide or placebo, in addition to insulin glargine for 40 weeks.

Here are results from each trial:

SURPASS-1
Baseline Characteristics: Most of the individuals (54%) had not previously used a diabetes medication, had lived with diabetes for less than five years, had an average A1C of 7.9% and a BMI of 32.
A1C	Weight Loss	Other Results
Tirzepatide led to an A1C decrease of 1.9 percentage points (with the 5 mg dose) up to 2.1 percentage points (with the 15 mg dose), compared to a 0.04 percentage point increase in the placebo group. More than 87% of participants in the tirzepatide groups achieved an A1C level below 7%	Participants lost an average of 15 to 21 pounds (or 7 to 9.5 kilos, with the 5 mg dose and 15 mg dose, respectively) with tirzepatide. In the placebo group, participants only lost on average about 1.5 pounds.	Fasting glucose levels went down by 44 to 49 mg/dL (with the 5 mg and 15mg dose of tirzepatide, respectively). At the 15 mg dose, tirzepatide reduced total cholesterol by 8.4%, triglycerides by 21%, and LDL “bad” cholesterol by 12.4%. It increased HDL “good” cholesterol by 7.5% from baseline. Participants on all three tirzepatide doses reported better overall health-related quality of life. People receiving the 10 mg and 15 mg doses also indicated significantly improved self-perception of body weight.
SURPASS-2
Baseline Characteristics: A1C levels between 7.0% and 10.5% and were taking only metformin at the start of the trial.
A1C	Weight Loss	Other Results
Tirzepatide reduced A1C by 2.1 percentage points (with the 5 mg dose) up to 2.5 percentage points (with the 15 mg dose). In comparison, people taking semaglutide saw a 1.9 percentage point decrease in A1C.	Tirzepatide reduced weight by 17 to 27 pounds (or 7.8 to 12.4 kilos, with the 5 mg dose and 15 mg dose, respectively). People taking semaglutide lost an average of 13.6 pounds (6.2 kilos). More than 78% of participants taking tirzepatide lost at least 5% of their weight, compared to 58% in the semaglutide group.	Tirzepatide helped people achieve an A1C below 7%. More than 85% of participants taking any dose of tirzepatide reached this threshold, compared to 81% of people taking semaglutide.
SURPASS-3
Baseline Characteristics: Participants had an average duration of diabetes of eight years, an A1C of 8.2%, weighed 207 lbs, and took metformin (some also took SGLT-2 inhibitor drugs).
A1C	Weight Loss	Other Results
A1C decreased by 1.9 percentage points (with the 5 mg dose) up to 2.4 percentage points (with the 15 mg dose) in those taking tirzepatide, compared to a 1.3 percentage point decrease in the insulin degludec group. More than 85% of people taking tirzepatide achieved an A1C below 7%, compared to 61% of those in the insulin group.	People taking tirzepatide lost 16.5 to 29 pounds (or 7.5 to 12.9 kilos, with the 5 mg and 15 mg dose, respectively). In the insulin degludec group, people saw a 5 pound (2.3 kilo) weight increase.	People taking tirzepatide experienced fewer instances of hypoglycemia (glucose levels below 70 mg/dL) than people taking insulin degludec.
SURPASS-5
Baseline Characteristics: Participants had an average duration of diabetes of 13 years, an A1C of 8.3%, weighed 209 lbs, and took 38 daily units of insulin (some also took metformin).
A1C	Weight Loss	Other Results
A1C decreased by 2.2 percentage points (with the 5 mg dose) up to 2.6 percentage points (with the 15 mg dose) for those taking tirzepatide, compared to a 0.9 percentage point increase in the placebo group. More than 93% of participants in the tirzepatide groups achieved an A1C level below 7%, compared to 34% of people in the placebo group.	Participants lost an average of 13.7 to 24 pounds (or 6.2 to 10.9 kilos, with the 5 mg dose and 15 mg dose of tirzepatide, respectively). In the placebo group, participants only lost 3.7 pounds.	N/A

Together, these results are extremely promising for tirzepatide and suggest that it may be a safe and highly effective treatment for both glucose management and weight loss in people with type 2 diabetes. As you can see the researchers compared several different doses of tirzepatide and if this drug becomes available, these studies will help people and their healthcare providers understand dosing for the drug, how different doses lead to varying levels of success, and how to use it in combination with other drugs to keep people healthy while still producing the desired results. We will continue to update you as this exciting new medication makes its way through the FDA approval process.

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