STEP-2: Semaglutide With Type 2 Diabetes
Last verified May 2026 · Phase 3 · Finished; published March 2021 · NCT03552757 ↗
Enrollment required a BMI of at least 27, a diabetes diagnosis at least 180 days old and HbA1c between 7.0% and 10.0%. That last criterion is worth noting — this was not a trial of well-controlled or newly diagnosed diabetes, and the result belongs to a population with meaningful hyperglycemia. The trial reported both weight and glycemic outcomes, and it is the basis for prescribing Wegovy rather than Ozempic to someone whose primary goal is weight but whose chart says type 2 diabetes.
- Enrollment
- 1,210
- Duration
- 68 weeks on treatment, the first 16 spent stepping the dose up, then 7 weeks off the drug to week 75
- Drug
- Semaglutide 2.4 mg (Wegovy)
- Population
- Adults 18 and over carrying a BMI of 27 or higher, whose type 2 diabetes had been diagnosed at least 180 days before, running an HbA1c of 7.0% to 10.0%, and managed either by diet and exercise alone or by up to three stable oral drugs — metformin, a sulfonylurea, an SGLT2 inhibitor, a glitazone. ⚠ Anyone on insulin was excluded. Average starting weight 99.8 kg at a BMI of 35.7, average HbA1c 8.1%, average age 55, half women, 61.8% white, and about eight years since diagnosis. Run at 149 sites in 12 countries from June 2018 to March 2020.
Primary endpoint
How much body weight came off over 68 weeks, on the 2.4 mg dose against placebo
Treatment arm
−9.6%
Comparator
−3.4%
Treatment difference: Estimated treatment difference −6.2 percentage points (95% CI −7.3 to −5.2; P<0.0001)
There was a second half to the endpoint: 68.8% on the 2.4 mg dose shed 5% of body weight or more, where 28.5% on placebo did. ⚠ Hold the headline figure next to STEP-1's 14.9% — same drug, same dose, same length of trial, five percentage points less. Diabetes is the difference.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| The weight dose against the diabetes dose, head to head ★ The most practically useful row here, because it is Wegovy's dose against Ozempic's in the same trial and the same patients. The higher dose bought about 2.7 more percentage points of weight. | −9.6% (2.4 mg) | −7.0% (1.0 mg) | Estimated treatment difference −2.7 percentage points (95% CI −3.7 to −1.6; P<0.0001) |
| Lost at least 5% of body weight Roughly seven in ten on the weight dose, closer to six in ten on the diabetes dose, and under three in ten on placebo. | 68.8% (2.4 mg); 57.1% (1.0 mg) | 28.5% (placebo) | Odds ratio 4.88 (95% CI 3.58 to 6.64) for 2.4 mg vs placebo; P<0.0001 |
| Lost at least a tenth of body weight ★ Five and a half times the placebo rate, in a population where older weight drugs barely separated from placebo at all. That is the real significance of this trial. | 45.6% (2.4 mg); 28.7% (1.0 mg) | 8.2% (placebo) | Odds ratio 7.41 (95% CI 4.95 to 11.08) for 2.4 mg vs placebo; P<0.0001 |
| Lost at least 15% ⚠ About a quarter got here, against half the participants in the non-diabetic trial. If 15% is your target, diabetes makes it materially less likely. | 25.8% (2.4 mg); 13.7% (1.0 mg) | 3.2% (placebo) | Odds ratio 7.65 (95% CI 4.44 to 13.20) for 2.4 mg vs placebo; P<0.0001 |
| Three-month average blood sugar ★ The two doses were indistinguishable on blood sugar — 1.6 against 1.5 points. That is the key to the dose question below: blood sugar tops out around the lower dose while weight keeps responding to more. | −1.6 (2.4 mg); −1.5 (1.0 mg) | −0.4 (placebo) | Estimated treatment difference −1.2 percentage points (95% CI −1.4 to −1.1) for 2.4 mg vs placebo; P<0.0001 |
| Inches off the waist About 9 cm, roughly 3.5 inches, against 4.5 cm on placebo. | −9.4 cm (2.4 mg) | −4.5 cm (placebo) | Estimated treatment difference −4.9 cm (95% CI −5.9 to −4.0); P<0.0001 |
| Top blood-pressure number Down about 3.4 points beyond placebo — smaller than the drop in the non-diabetic trial, in line with the smaller weight change. | −3.9 mmHg (2.4 mg) | −0.5 mmHg (placebo) | Estimated treatment difference −3.4 mmHg (95% CI −5.6 to −1.3); P=0.0016 |
| Blood sugar after an overnight fast A drop of roughly 35 mg/dL beyond placebo. Unlike the non-diabetic trials, this is treatment of something rather than movement inside the normal range. | −43.8 mg/dL (2.4 mg) | −8.5 mg/dL (placebo) | Estimated treatment difference approximately −35 mg/dL (95% CI −41 to −29); P<0.0001 |
| How people rated their own physical functioning, on a weight-specific questionnaire The drug group cleared the threshold usually treated as a real-world improvement; the placebo group did not. | +14.1 points (2.4 mg) | +8.7 points (placebo) | Estimated treatment difference 5.3 points (95% CI 2.8 to 7.9); P<0.0001 |
| Triglycerides, a blood fat Down about 22% against 7% on placebo. | 0.78 (2.4 mg; 22% relative reduction) | 0.93 (placebo; 7% relative reduction) | Estimated treatment ratio 0.84 (95% CI 0.79 to 0.89); P<0.0001 |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Nausea The leading complaint, usually mild to moderate and bunched into the weeks when the dose was rising. The 1.0 mg dose produced it in 25.6%. | 33.7% (sema 2.4 mg) | 11.4% (placebo) |
| Diarrhea Similar at both doses — 19.0% at 1.0 mg. | 21.5% (sema 2.4 mg) | 7.4% (placebo) |
| Vomiting ★ This one does scale with dose: 12.4% at 1.0 mg against 20.9% at 2.4 mg. Part of what the extra weight loss costs. | 20.9% (sema 2.4 mg) | 5.4% (placebo) |
| Constipation Roughly twice the placebo rate. | 17.8% (sema 2.4 mg) | 8.2% (placebo) |
| Indigestion Five times the placebo rate, though uncommon in absolute terms. | 8.7% (sema 2.4 mg) | 1.7% (placebo) |
| Confirmed low blood sugar with symptoms ⚠ This is the row that matters if you have diabetes and it does not appear in the non-diabetic trials at all. Severe episodes were rare either way, and the excess sat almost entirely in people also taking a sulfonylurea — a known combination risk. If you are on one, this is a conversation to have before starting. | 5.7% (sema 2.4 mg) | 3.0% (placebo) |
| Diabetic eye disease ⚠ Slightly higher than placebo without reaching significance. It echoes the signal seen in other semaglutide diabetes trials, where rapidly dropping blood sugar appears to be the trigger rather than the drug itself. Existing retinopathy is a reason for an eye check before starting. | 3.2% (sema 2.4 mg) | 2.7% (placebo) |
| Gallstones Five times the placebo rate. Losing weight quickly does this regardless of the method. | 2.5% (sema 2.4 mg) | 0.5% (placebo) |
| Stopped the drug over a side effect 6.7% at the weight dose against 5.2% at the diabetes dose and 3.5% on placebo, almost all of it stomach and bowel trouble during dose escalation. | 6.7% (sema 2.4 mg) | 3.5% (placebo) |
| Serious adverse events of any kind Close to the placebo rate. | 9.1% (sema 2.4 mg) | 7.9% (placebo) |
Clinical significance
STEP-2 is the pivotal support for using Wegovy in a diabetes population and the reference point for setting expectations there. Its practical value is as a corrective: a reader with diabetes reading STEP-1's 14.9% is reading a number from a trial that excluded them. ⚠ The HbA1c improvement is real and secondary — this was a weight trial, not a glycemic-control trial, and the diabetes-specific evidence for semaglutide sits in the SUSTAIN program.
Who sells semaglutide, and for how much
This trial tested Semaglutide 2.4 mg (Wegovy). Across the 556 sellers on this register, 283 publish a standing monthly cash price for compounded semaglutide, from $79 a month, with a median of $174.
⛔ None of those sellers was in this trial. A compounded preparation is not the product studied here: no agency has reviewed that specific preparation for safety, effectiveness or manufacturing quality, and its concentration is set by whichever pharmacy filled it. The result above is the strongest evidence available for semaglutide and it was generated on something else. Every seller, with its price record.
Frequently Asked Questions
References
- 1.Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I; STEP 2 Study Group. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021. PMID: 33667417.
- 2.U.S. National Library of Medicine. Research Study Investigating How Well Semaglutide Works in People With Type 2 Diabetes Suffering From Overweight or Obesity (STEP 2). ClinicalTrials.gov, NCT03552757. 2021. https://clinicaltrials.gov/study/NCT03552757
- 3.Wilding JPH, Batterham RL, Calanna S, et al.; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021. PMID: 33567185.
- 4.Garvey WT, Frias JP, Jastreboff AM, et al.; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023. PMID: 37315391.
- 5.U.S. Food and Drug Administration. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014 (Wegovy approval announcement). FDA News Release, June 4, 2021. 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014