Study Finds Lilly’s Tirzepatide Reduces A1C and Body Weight


Editor’s Note: This article was updated on 2/09/22 and adds to our ongoing coverage of Tirzepatide, a potential new treatment for people with type 2 diabetes that is currently in development in clinical trials. 

On February 8th, 2022, the Journal of the American Medical Association published results from the SURPASS-5 clinical trial showing tirzepatide leads to greater improvements in improving A1C and body weight when used as an add-on to insulin glargine (long-acting insulin) compared to using insulin glargine, alone. At the end of the 40-week trial, participants’ A1C lowered by:

  • 2.11 percent when given 5 mg of Tirzepatide.
  • 2.4 percent when given 10 mg of Tirzepatide.
  • 2.34 percent when given 15 mg of Tirzepatide.
  • 0.86 percent when only given a placebo.

Tirzepatide’s impact on body weight resulted in:

  • 5.4 kg (11.9 lbs) of weight loss with 5 mg of Tirzepatide.
  • 7.5 kg (16.5 lbs) of weight loss with 10 mg of Tirzepatide.
  • 8.8 kg (19.4 lbs) of weight loss with 15 mg of Tirzepatide.
  • 1.6 kg (3.5 lbs) when only given a placebo.

These latest results continue to show Tirzepatide’s impact on blood glucose levels and body weight in patients with type 2 diabetes when compared with other, established treatments. For previous findings during this trial, please read previous updates below.

Other Tirzepatide Clinical Trial Updates:

At the 57th European Association for Study of Diabetes (EASD) annual meeting, Lilly Diabetes announced tirzepatide led to better time-in-range (TIR) numbers compared to people with type 2 diabetes who use insulin degludec, an ultra long-acting basal insulin, in the SURPASS-3 study.  Time-in-range is the percentage of time spent between 70-180 mg/dL; it’s recommended people with diabetes maintain a TIR of at least 70 percent, spend less than 4 percent of time below 70 mg/dL, and less than 25 percent above 180 mg/dL. Time-in-range is a metric provided by a continuous glucose monitor (CGM).

In the new findings, participants taking 15mg of tirzepatide experienced a 91.2 percent time-in-range compared to 75 percent who took insulin degludec. Another notable effect of the study is that the patients on tirzepatide also spent less time in hypoglycemia.

“The CGM data collected through this SURPASS-3 sub-study show that tirzepatide helped participants have less variability in their blood glucose levels throughout the day, including spending less time below target range and more time in a tighter target range reflecting a normal blood glucose range,” said Richard Bergenstal, M.D., Executive Director of the International Diabetes Center at Park Nicollet. “Improving glycemic variability, increasing time in range and reducing time below range are important metrics in the management of type 2 diabetes because they reflect blood glucose control throughout the day, offering context beyond the three-month average of A1C.”

In a separate report from EASD, Lilly Diabetes also announced that after 52 weeks of use, tirzepatide improves liver fat content compared to insulin degludec, in addition to reductions of visceral adipose tissue (visceral fat) and abdominal subcutaneous adipose tissue (subcutaneous fat). Visceral and subcutaneous fat is associated with insulin resistance and increased risks of heart disease and blood pressure. Compared to tirzepatide, the participants who took insulin degludec had increases in both measurements.

“Increased ectopic fat—such as liver fat or visceral adipose tissue—is commonly seen in adults with type 2 diabetes and is associated with an inflammatory response and increased cardiometabolic risk,” said Amalia Gastaldelli, Ph.D., Research Director of Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa Italy. “We are encouraged by the robust reductions in liver fat content and abdominal adipose tissue observed with all three doses of tirzepatide in this population of adults with type 2 diabetes and elevated liver fat content.”

Lilly Diabetes reported that in the 52-week SURPASS-4 clinical trials, the largest and longest of the programs to date, the highest dose of tirzepatide (15 mg) led to significant A1C and bodyweight reduction in adults with type 2 diabetes. With the highest dose of tirzepatide, 91 percent of participants achieved an A1C that was less than seven percent.

SURPASS-4 isn’t the only clinical trial that’s shown positive results. The other clinical trial, SURPASS-3, a 52-week study, also showed the highest dose of tirzepatide (15 mg) reduced A1C 2.37 percent and body weight by 12.9 kg/28.4 lbs. In SURPASS-3, participants who received the highest dose and on average, have had diabetes for a little over 13 years, achieved an A1C of less than 5.7 percent—the level seen in people without diabetes.

In both studies, the overall safety profile is similar to that of a glucagon-like peptide (GLP-1 1) receptor agonist. Side effects were reported, with gastrointestinal side effects being the most commonly reported.

John Doupis, MD, PhD, director of the diabetes division and clinical research center at the Latriko Paleou Falirou Medical Center, provided remarks on the latest findings and acknowledged the importance of tirzepatide’s impact on managing type 2 diabetes. “Tirzepatide delivered impressive results in this study, providing superior A1c reductions compared to insulin glargine–as well as the addition of significant weight loss–in people with type 2 diabetes who have increased cardiovascular risk,” Doupis said in a news release.

Tirzepatide “is a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single novel molecule.” In other words, tirzepatide works by decreasing food intake and increasing energy output which works in tandem to generate weight loss and regulate blood glucose levels. This also marks the first-ever dual GIP-GLP combo drug used for type 2 treatment.

These new findings are similar to the results published in February when Lilly Diabetes reported tirzepatide significantly reduced A1C and body weight in adults with type 2 diabetes. Participants who used the highest dose of tirzepatide reduced A1Cs by 2.37 percent and body weight by 12.9 percent; about 50 percent of patients in this study achieved an A1C of less than 5.7 percent.

The study observed that each of the tirzepatide doses led to lower A1Cs and reducded body weight. Lilly reported the following:

  • A1C reduction: -2.11 percent (5 mg), -2.30 percent (10 mg), -2.41 percent (15 mg), -1.39 percent (placebo)
  • Weight reduction: -6.4 kg (5 mg), -8.9 kg (10 mg), -10.6 kg (15 mg), +1.7 kg (placebo)
  • Percentage of participants achieving A1C <7 percent: 75.1 percent (5 mg), 82.9 percent (10 mg), 84.9 percent (15 mg), 48.8 percent (placebo)

The safety of tirzepatide was consistent with the glucagon-like peptide-1 (GLP-1). Side effects were reported with gastrointestinal being the most commonly reported.

Currently, tirzepatide is in its fifth and final study for blood glucose management in adults with type 2 diabetes. SURPASS-4 included 2,002 study participants from the United States, Canada, Brazil, Australia and Israel; patients were either given 5 mg, 10 mg, or 15mg of tirzepatide or a placebo (no treatment) in a 1:1:1:3 ratio during a 52-week period. This was done in order to demonstrate that using tirzepatide, especially higher doses of the medication, resulted in a greater outcome for A1C and body weight reductions opposed to no treatment.

“These strong results reinforce our belief that tirzepatide has the potential to be an exciting treatment for people living with type 2 diabetes,” said Mike Mason, president of Lilly Diabetes in a press release. “We look forward to meeting our goal of bringing an important new therapy to people living with this condition, including sharing more detailed results at scientific congresses and submitting to regulatory authorities later this year.”

WRITTEN BY Makaila Heifner, POSTED 01/08/21, UPDATED 12/12/22

Makaila was diagnosed with Type 1 diabetes at 16 months old. Before joining the Beyond Type 1 team in 2019, she worked at several diabetes camps, including Camp Leo and DYF. Makaila earned her BA in Global Studies and a minor in Public Policy from the University of California, Berkeley. When she isn’t editing articles, Makaila is a fan of soup, public radio, and live music. Check her out on Instagram: @makailaheifner