The short answer: Retatrutide lowered A1C by about 1.4 to 2.0 percentage points in people with type 2 diabetes across phase 2 and phase 3 trials. In the phase 2 obesity trial, 72% of people with prediabetes reached normal A1C, compared with 22% on placebo. Trials reported no severe hypoglycemia. Retatrutide is investigational and not FDA approved, so all of these numbers come from clinical trials.

What happened to A1C in the phase 2 diabetes trial?

The first large test in type 2 diabetes was a 36-week phase 2 trial run at 42 US sites. Rosenstock and colleagues published it in The Lancet in 2023. It enrolled 281 adults with an A1C of 7.0% to 10.5% and a BMI of 25 to 50. Participants used diet and exercise alone or a stable dose of metformin.

The primary endpoint was the change in A1C at 24 weeks. The results by group were:

  • Retatrutide 0.5 mg: -0.43%
  • Retatrutide 4 mg: -1.30% to -1.39%, depending on the starting dose
  • Retatrutide 8 mg: -1.88% to -1.99%, depending on how fast the dose went up
  • Retatrutide 12 mg: -2.02%
  • Dulaglutide 1.5 mg (Trulicity): -1.41%
  • Placebo: -0.01%

Every dose of 4 mg or more beat placebo. The 8 mg slow escalation group and the 12 mg group also beat dulaglutide. The authors said the findings were consistent at 36 weeks.

A summary in ADA Meeting News reported that up to 82% of participants reached an A1C below 6.5%. Up to 31% reached an A1C below 5.7%, which is the normal range.

What did the first phase 3 diabetes trial show?

The diabetes phase 3 program is called TRANSCEND-T2D. Its first trial, TRANSCEND-T2D-1 (NCT06354660), is complete. Lilly announced topline results on March 19, 2026. The full paper appeared in The Lancet in June 2026.

The trial ran for 40 weeks at 48 sites in the USA, Mexico and India. It randomized 537 adults whose diabetes was not controlled by diet and exercise alone. They took no other diabetes drugs. Mean baseline A1C was 7.9%, and people had had diabetes for 2.5 years on average.

Using the treatment-regimen estimand, which counts everyone regardless of whether they stayed on the drug, A1C changed by:

  • -1.69% with retatrutide 4 mg
  • -1.86% with retatrutide 9 mg
  • -1.94% with retatrutide 12 mg
  • -0.81% with placebo

The difference from placebo was about 0.9 to 1.1 points. Lilly's efficacy estimand, which models people who stayed on treatment, gave reductions of up to 2.0%. Weight fell by up to 15.3% on the treatment-regimen estimand.

Two more trials in the program are still running. According to ClinicalTrials.gov, TRANSCEND-T2D-2 compares retatrutide with semaglutide in people on metformin, with or without an SGLT2 inhibitor. TRANSCEND-T2D-3 tests retatrutide in people with moderate or severe kidney impairment who use basal insulin. Both are listed as active, not recruiting. Our 2026 trials tracker lists the rest of the program.

How does A1C change in people with obesity and type 2 diabetes?

TRIUMPH is Lilly's obesity program, but one of its trials enrolled people with diabetes. TRIUMPH-2 topline results came out on July 23, 2026. The trial randomized 1,152 adults with type 2 diabetes and obesity or overweight for 80 weeks.

Weight loss was the primary endpoint. A1C change was a key secondary endpoint. From a baseline A1C of 7.7%, A1C fell by 1.4% with 4 mg, 1.6% with 9 mg and 1.5% with 12 mg. It fell by 0.2% with placebo. Weight fell by up to 20.8%.

These A1C drops are a little smaller than in TRANSCEND-T2D-1. The baseline A1C was also lower, and the two trials enrolled different people. These are topline figures from a press release. The full paper has not yet been published.

TRIUMPH-3 enrolled adults with severe obesity and heart disease, with or without diabetes. Lilly reported hyperglycemia as an adverse event in 3.9% (9 mg) and 3.1% (12 mg) of retatrutide users. The rate was 13.4% with placebo.

What about people with prediabetes or normal blood sugar?

The 48-week phase 2 obesity trial in the New England Journal of Medicine enrolled 338 adults with obesity or overweight. People with type 2 diabetes were not the focus of that trial. Retatrutide improved A1C, fasting glucose and insulin levels at weeks 24 and 48.

Some participants started with prediabetes. At week 48, 72% of them on retatrutide had an A1C below 5.7%. Only 22% on placebo did. A 2024 review in npj Metabolic Health and Disease and a 2024 report in Health Science Reports both cite these figures.

In people with normal blood sugar, the drug does not appear to push glucose down much. A 2025 review in Biomolecules describes the phase 1 study in 45 healthy people. Changes in fasting glucose with retatrutide were similar to placebo.

TRIUMPH-1 enrolled only people without diabetes. Lilly's topline release reported weight and heart risk factor results, but it did not report glucose data.

Why does the glucagon arm not raise blood sugar?

This is a fair question. Glucagon is the hormone that raises blood sugar. The Biomolecules review explains that glucagon tells the liver to make new glucose and to break down stored glycogen. On its own, that raises blood glucose.

Retatrutide does not act on glucagon receptors alone. It also activates GLP-1 and GIP receptors. These incretin pathways increase insulin release after meals, reduce appetite and slow stomach emptying. Our triple agonist explainer covers the receptor biology in more detail.

Lilly scientists described the balance in the 2022 Cell Metabolism paper that introduced the molecule. In lab tests, it showed balanced glucagon and GLP-1 receptor activity, with more GIP receptor activity. In obese mice it improved glycemic control. The glucagon arm added energy expenditure on top of the drop in food intake.

The human trials answer the question in practice. In every diabetes trial above, the net effect on A1C was downward. Large weight loss likely helps too, since weight loss improves insulin sensitivity.

Does retatrutide cause low blood sugar?

Severe hypoglycemia has not been a signal so far. The phase 2 diabetes paper reported no severe hypoglycemia and no deaths. The TRANSCEND-T2D-1 paper also reported no severe hypoglycemia.

There are two limits to that reassurance. First, TRANSCEND-T2D-1 enrolled people on no other diabetes drugs, and the phase 2 trial allowed only metformin. Neither drug commonly causes low blood sugar on its own. Second, results from TRANSCEND-T2D-3, the trial in people using basal insulin, are not out yet.

The approved drugs in this class carry a clear warning. Lilly's safety information for tirzepatide (Zepbound) says the risk of low blood sugar may be higher with a sulfonylurea or insulin. It is reasonable to expect the same caution for retatrutide. Any label would come only after FDA review.

If you already take insulin or a sulfonylurea, talk with your clinician before joining a trial. Doses of those drugs sometimes need changes as weight and A1C fall.

The bottom line

Retatrutide lowered A1C by roughly 1.4 to 2.0 points in people with type 2 diabetes, with no severe hypoglycemia reported. In people with prediabetes, most reached a normal A1C in phase 2. The glucagon arm does not cancel out the glucose-lowering effect. Retatrutide is still investigational and not FDA approved. Lilly plans to file first for obesity, knee osteoarthritis pain and sleep apnea, not diabetes. Our FDA approval timeline tracks that filing. For approved options today, see mounjaro.md on tirzepatide.

Last updated: September 2026. This article is for informational purposes only and does not constitute medical advice. Retatrutide is available only in clinical trials. Talk with your clinician before changing any diabetes medication.