SCALE Diabetes: Liraglutide With Type 2 Diabetes
Last verified May 2026 · Phase 3 · Finished; published August 2015 · NCT01272232 ↗
Two active doses in one trial is a useful design, because it shows the drug's effect scaling rather than simply exceeding placebo. The gap between 1.8 mg and 3.0 mg here is the same pattern later seen across semaglutide and tirzepatide dose ladders, and it is the reason titration to a target dose matters clinically — and the reason dose-based pricing matters commercially, since the effective dose is the expensive one.
- Enrollment
- 846
- Duration
- 56 weeks of treatment plus 12 weeks off the drug, with observation to week 68
- Drug
- Liraglutide 3.0 mg (Saxenda)
- Population
- Adults 18 and over whose type 2 diabetes was handled by diet, by metformin, by a sulfonylurea or by some mixture of those — ⚠ nobody on insulin or another drug in this class was eligible — with a BMI of at least 27 and an HbA1c between 7.0% and 10.0%. Of the 846 randomized: average age 55, half women, 84% white, average weight 105.7 kg at a BMI of 37.1, average HbA1c 7.9%, and about seven years since diagnosis. Run at 126 sites across nine countries between June 2011 and January 2013.
Primary endpoint
How much body weight came off over 56 weeks, at each dose
Treatment arm
-6.0% (liraglutide 3.0 mg)
Comparator
-2.0% (placebo); -4.7% (liraglutide 1.8 mg)
Treatment difference: Estimated treatment difference liraglutide 3.0 mg vs placebo -4.00 percentage points (95% CI -5.10 to -2.90; P<0.001); liraglutide 3.0 mg vs 1.8 mg -1.34 percentage points (95% CI -2.10 to -0.57; P<0.001)
★ The endpoint also counted who cleared the thresholds: 54.3% lost at least 5% on the 3.0 mg dose against 40.4% on 1.8 mg and 21.4% on placebo, and 25.2% lost more than 10% against 15.9% and 6.7%. ⚠ Set the 6.0% next to the roughly 8% the same drug produced in people without diabetes and you have the diabetes penalty, measured in the same program.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| Lost at least 5% of body weight More than half at the higher dose, in a population where weight loss is consistently harder to achieve. | 54.3% (liraglutide 3.0 mg) | 21.4% (placebo); 40.4% (liraglutide 1.8 mg) | Estimated odds ratio liraglutide 3.0 mg vs placebo 4.8 (95% CI 3.4 to 6.8; P<0.001) |
| Lost more than a tenth of body weight About one in four at the higher dose, nearly four times the placebo rate. | 25.2% (liraglutide 3.0 mg) | 6.7% (placebo); 15.9% (liraglutide 1.8 mg) | Estimated odds ratio liraglutide 3.0 mg vs placebo 4.7 (95% CI 2.9 to 7.6; P<0.001) |
| Three-month average blood sugar ★ Note this is far larger than the same drug produces in people without diabetes — because there is real disease to treat here, starting from an average of 7.9%. When someone has diabetes, the blood-sugar benefit is often the bigger prize and the weight is the bonus. | -1.3 (liraglutide 3.0 mg) | -0.3 (placebo); -1.1 (liraglutide 1.8 mg) | Estimated treatment difference liraglutide 3.0 mg vs placebo -0.9 percentage points (95% CI -1.1 to -0.8; P<0.001) |
| Blood sugar after an overnight fast ⚠ Down about 38 mg/dL at the top dose — and note the 1.8 mg dose captured nearly all of it. Blood sugar tops out at the lower dose while weight keeps responding to more. | -38.0 mg/dL (liraglutide 3.0 mg) | -7.7 mg/dL (placebo); -34.7 mg/dL (liraglutide 1.8 mg) | Estimated treatment difference liraglutide 3.0 mg vs placebo -30.3 mg/dL (95% CI -36.1 to -24.6; P<0.001) |
| Got blood sugar under the standard 7% target More than two thirds at the higher dose, against just over a quarter on placebo. | 69.2% (liraglutide 3.0 mg) | 27.2% (placebo); 60.5% (liraglutide 1.8 mg) | Estimated odds ratio liraglutide 3.0 mg vs placebo 6.4 (95% CI 4.5 to 9.1; P<0.001) |
| Inches off the waist About 6 cm at the higher dose against 2.8 on placebo. | -6.0 cm (liraglutide 3.0 mg) | -2.8 cm (placebo); -4.9 cm (liraglutide 1.8 mg) | Estimated treatment difference liraglutide 3.0 mg vs placebo -3.2 cm (95% CI -4.2 to -2.2; P<0.001) |
| Top blood-pressure number A modest extra reduction, in line with what the rest of this drug's program showed. | -3.0 mmHg (liraglutide 3.0 mg) | -0.4 mmHg (placebo); -2.6 mmHg (liraglutide 1.8 mg) | Estimated treatment difference liraglutide 3.0 mg vs placebo -2.6 mmHg (95% CI -4.6 to -0.6; P=0.01) |
| Triglycerides, a blood fat ⚠ Down about 13% at the higher dose, tracking the weight. Cholesterol barely moved, which is the pattern across this whole class — these are not lipid drugs. | -13.4% (liraglutide 3.0 mg) | -3.3% (placebo); -8.7% (liraglutide 1.8 mg) | Estimated treatment ratio favoring liraglutide 3.0 mg vs placebo (P<0.001) |
| How people rated their own quality of life, on a weight-specific questionnaire ⚠ Better on the drug — and the placebo group improved 5.3 points too. Structured attention moves these scores on its own, which is why a control group matters. | +9.0 points (liraglutide 3.0 mg) | +5.3 points (placebo); +7.5 points (liraglutide 1.8 mg) | Estimated treatment difference liraglutide 3.0 mg vs placebo +3.7 points (95% CI +1.6 to +5.8; P<0.001) |
| Self-rated physical health on a general questionnaire A smaller improvement than the weight-specific questionnaire found — a recurring pattern worth noticing, since which instrument you choose changes the size of the answer. | +3.3 points (liraglutide 3.0 mg) | +1.4 points (placebo); +2.6 points (liraglutide 1.8 mg) | Estimated treatment difference liraglutide 3.0 mg vs placebo +1.9 points; nominal P<0.001 |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Any stomach or bowel problem Roughly 59% at the top dose against 33% on placebo, bunched into the four weeks while the dose climbed from 0.6 mg to 3.0 mg, and mostly mild and temporary. | 59.4% (liraglutide 3.0 mg); 53.2% (liraglutide 1.8 mg) | 33.2% (placebo) |
| Nausea ★ About a third at the top dose against 11% on placebo — and notably lower than the same drug produced in people without diabetes, who tend to tolerate it less well. | 33.1% (liraglutide 3.0 mg); 27.5% (liraglutide 1.8 mg) | 10.6% (placebo) |
| Diarrhea About 21% against 8.5% on placebo. | 21.4% (liraglutide 3.0 mg); 19.7% (liraglutide 1.8 mg) | 8.5% (placebo) |
| Vomiting About 13% at the top dose against under 4% on placebo, and rising with dose. | 12.9% (liraglutide 3.0 mg); 9.2% (liraglutide 1.8 mg) | 3.7% (placebo) |
| Constipation Barely above the placebo rate. | 11.6% (liraglutide 3.0 mg); 8.0% (liraglutide 1.8 mg) | 8.5% (placebo) |
| Indigestion About four times the placebo rate, though uncommon overall. | 8.5% (liraglutide 3.0 mg); 6.6% (liraglutide 1.8 mg) | 1.9% (placebo) |
| Headache ★ Identical to placebo — a useful control within the table, showing that not everything reported during a trial is caused by the drug. | 10.0% (liraglutide 3.0 mg); 7.8% (liraglutide 1.8 mg) | 10.1% (placebo) |
| Confirmed low blood sugar with symptoms ⚠ The row that matters most if you have diabetes and does not appear in the non-diabetic trials. Higher than placebo, because sulfonylureas were permitted — and the protocol required halving the sulfonylurea dose at randomization, which reduced the risk without removing it. ★ No severe episodes needing someone else's help occurred in any arm. If you take a sulfonylurea, that dose reduction is the conversation to have before starting. | 21.8% (liraglutide 3.0 mg); 27.0% (liraglutide 1.8 mg) | 16.9% (placebo) |
| Gallstones About three times the placebo rate. Losing weight quickly does this whatever the method. | 1.4% (liraglutide 3.0 mg); 1.4% (liraglutide 1.8 mg) | 0.5% (placebo) |
| Pancreatitis, confirmed ⚠ One case, on the top dose. A single event proves nothing on its own, and it is the kind of event that keeps the class-level pancreatitis warning on the label. | 0.2% (1/423, liraglutide 3.0 mg); 0% (liraglutide 1.8 mg) | 0% (placebo) |
| Stopped the drug for good over a side effect 9.7% at the top dose against about 5% at the lower dose and on placebo, mostly during or just after the dose increases. | 9.7% (liraglutide 3.0 mg); 4.9% (liraglutide 1.8 mg) | 4.7% (placebo) |
| Any serious adverse event Close to the placebo rate, with nothing clustering apart from the gallbladder events and the isolated pancreatitis case. | 9.7% (liraglutide 3.0 mg); 6.6% (liraglutide 1.8 mg) | 7.5% (placebo) |
Subgroup analyses
- People already taking a sulfonylurea: Halving that dose at the start reduced the risk of lows without weakening the weight or blood-sugar benefit
★ A protocol decision that has since become standard practice: when a GLP-1 goes in, the sulfonylurea comes down.
- How high blood sugar was to start with: Bigger blood-sugar reductions in those who started higher, with weight loss much the same either way
Expected of any diabetes drug — there is more to correct when there is more wrong.
- Women against men: Somewhat more weight loss in women, with blood-sugar effects the same
★ Worth noting that this trial was 50% women, unusually balanced for an obesity trial — a consequence of recruiting a diabetes population rather than a weight-clinic one.
Clinical significance
This trial supports Saxenda's use in diabetes with obesity and demonstrates dose-response cleanly. Its practical relevance today is limited: −6.0% is well below what the weekly drugs deliver, and Saxenda's pricing is not competitive with them. ⚠ It remains useful as evidence of the diabetes penalty — the same drug in people without diabetes reached about −8.0% in SCALE Obesity.
Who sells liraglutide, and for how much
This trial tested Liraglutide 3.0 mg (Saxenda). Across the 556 sellers on this register, 3 publish a standing monthly cash price for compounded liraglutide, from $160 a month, with a median of $214.
⛔ 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 liraglutide and it was generated on something else. Every seller, with its price record.
Frequently Asked Questions
References
- 1.Davies MJ, Bergenstal R, Bode B, et al.; NN8022-1922 Study Group. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA. 2015. PMID: 26284720.
- 2.Novo Nordisk A/S. Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes: SCALE - Diabetes (NCT01272232). ClinicalTrials.gov. 2015. https://clinicaltrials.gov/study/NCT01272232
- 3.Pi-Sunyer X, Astrup A, Fujioka K, et al.; SCALE Obesity and Prediabetes NN8022-1839 Study Group. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015. PMID: 26132939.
- 4.Davies M, Færch L, Jeppesen OK, et al.; 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.
- 5.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: 37385275.
- 6.Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Steering Committee. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016. PMID: 27295427.
- 7.Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022. PMID: 35441470.