SCALE Maintenance: Holding On to a Loss
Last verified November 2026 · Phase 3 · Finished; published November 2013 · NCT00781937 ↗
Maintenance is where most weight-loss attempts fail, and it is the phase least studied because trials are usually built around the losing part. Putting the diet first and the drug afterwards isolates maintenance, and the trial reports both continued loss on the drug and a flat placebo arm rather than the regain seen when a drug is withdrawn. Read alongside STEP-4, the picture is consistent: the drug does work during maintenance, and removing it moves weight back.
- Enrollment
- 422
- Duration
- 56 weeks of randomized treatment following a 4 to 12 week diet run-in, then 12 weeks off the drug with observation to week 68
- Drug
- Liraglutide 3.0 mg (Saxenda)
- Population
- Adults 18 and over without diabetes whose BMI was 30 or more (or at least 27 alongside high blood pressure or abnormal cholesterol) and who had shed 5% or more of their weight during a run-in on 1,200 to 1,400 calories a day. Only people the diet worked for went forward. Of the 422 randomized: average age 46, 81% women, 84% white, average weight 99.6 kg after a mean 6.0% run-in loss, average BMI 35.6. Run at sites in the United States and Canada between October 2008 and September 2010, per the trial's ClinicalTrials.gov record.
The Saxenda drug page covers the drug itself: its dosing, cost and side effects.
Primary endpoint
How much MORE weight came off across 56 weeks, after the diet had already worked
Treatment arm
−6.2%
Comparator
−0.2%
Treatment difference: Estimated treatment difference −6.1 percentage points (95% CI −7.5 to −4.6; P<0.0001)
Two different findings sit in this one line. The drug group kept losing, another 6.2%, reaching roughly 12% below where they started. The placebo group, still receiving support, went essentially flat rather than regaining. Holding a diet-induced loss for a year is itself an achievement, and the drug turned holding into continued progress.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| Lost at least another 5% on top of the diet loss Half the drug group against about a fifth on placebo. | 50.5% (107/212) | 21.8% (45/206) | Estimated odds ratio 3.9 (95% CI 2.4 to 6.1; P<0.0001) |
| Lost at least another 10% Roughly four times as many: 26.1% against 6.3%, per the trial's ClinicalTrials.gov results. | 26.1% | 6.3% | Estimated odds ratio 5.3 (95% CI 2.8 to 10.1; P<0.0001) |
| Still holding everything the diet had achieved, a year later This row answers the question the trial was built for. Four in five held or improved on the drug, against fewer than half on placebo. If keeping the loss is the goal, this is the number to remember. | 81.4% | 48.9% | P<0.0001 |
| Weight change in kilograms About 6 kg more off, against essentially nothing on placebo. | −5.7 kg | +0.2 kg | Estimated treatment difference −5.9 kg (95% CI −7.3 to −4.4), per the registry results |
| Inches off the waist Kept falling on the drug and barely moved on placebo, following the same pattern as the scale. Figures are per the trial's ClinicalTrials.gov results. | −4.4 cm | −0.9 cm | Estimated treatment difference −3.5 cm (95% CI −4.8 to −2.2; P<0.0001) |
| Top blood-pressure number Per the trial's ClinicalTrials.gov results, the top number crept back up in both arms after the diet run-in, by less on the drug. Most of the blood-pressure benefit had already happened during the diet run-in, before anyone took a drug, so be wary when a drug gets credit for the whole effect. | +1.3 mmHg | +4.0 mmHg | Estimated treatment difference −2.7 mmHg (95% CI −4.7 to −0.8; P=0.007) |
| Total cholesterol Basically identical between the arms, and both slightly up. As with blood pressure, the diet had already done the lipid work. | +1.6% | +2.4% | Estimated treatment difference −0.8% (not statistically significant) |
| Three-month average blood sugar Nobody here had diabetes, so this moves inside the normal-to-prediabetic band. Figures are per the trial's ClinicalTrials.gov results. | −0.14 | +0.13 | Estimated treatment difference −0.27 percentage points (95% CI −0.33 to −0.21; P<0.0001) |
| Fat mass specifically, measured by body scan The scan substudy makes this trial more informative than the scale alone. The extra weight was overwhelmingly fat, with the balance of lean to fat tissue preserved. Not every trial of this era checked. | −15.4% | −4.5% | Estimated treatment difference favoring liraglutide; P<0.0001 |
| How many developed type 2 diabetes Two cases against four, far too few to conclude anything. It is a hint, and a much larger dedicated prevention trial later confirmed the direction. | 0.9% (2/212) | 1.9% (4/210) | Numerically lower on liraglutide; underpowered for formal inference in this trial. |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Any stomach or bowel problem Nearly three quarters of the drug group. The problems bunched into the four weeks while the dose climbed from 0.6 mg to 3.0 mg, and were mostly mild to moderate and temporary, but that is a high rate however you frame it. | 74.1% (157/212) | 43.8% (92/210) |
| Nausea Almost half the drug group against 17% on placebo, peaking during dose increases and easing after. The nausea, diarrhea, constipation, vomiting, headache and serious-event rows are per the trial's ClinicalTrials.gov results. | 47.6% (101/212) | 17.1% (36/210) |
| Diarrhea About 18% against 12%. | 17.9% (38/212) | 12.4% (26/210) |
| Constipation About 27% against 12%. | 26.9% (57/212) | 12.4% (26/210) |
| Vomiting About seven times the placebo rate. | 16.5% (35/212) | 2.4% (5/210) |
| Headache No different from placebo, one of the few complaints not attributable to the drug. | 12.7% (27/212) | 12.4% (26/210) |
| Reaction where the injection went in Close to the placebo rate, because injecting anything daily produces some of this. | 13.7% (29/212) | 10.5% (22/210) |
| Low blood sugar with symptoms Five cases against none, all minor, with no severe episodes in either group, in people who did not have diabetes. | 2.4% (5/212) | 0.0% (0/210) |
| Gallstones and gallbladder inflammation Five cases against none. Losing weight quickly causes this whatever the method, and it shows up across every trial in this class. | 2.4% (5/212) | 0.0% (0/210) |
| Stopped the drug for good over a side effect 9.9% against 3.8%, mostly during or just after the dose increases. | 9.9% (21/212) | 3.8% (8/210) |
| Any serious adverse event 4.2% against 2.4%, with nothing clustering except the gallbladder events noted above. | 4.2% (9/212) | 2.4% (5/210) |
Subgroup analyses
- People who arrived with prediabetes: Fewer still met the criteria for prediabetes a year later on the drug
A planned analysis, and the signal a much larger dedicated prevention trial later confirmed at scale.
- People for whom the diet had worked unusually well, losing 10% or more before starting: They kept losing on the drug too, in line with everyone else
This rules out an obvious objection: the benefit is not confined to people who had further to go.
- Women against men: Same direction in both
81% of this trial was women, so the male group is small and no formal comparison is possible.
Clinical significance
The practical reading is that maintenance is an active phase requiring continued treatment rather than a coasting period, which has direct bearing on how long anyone should budget for. Liraglutide is largely displaced commercially, so the drug here is not the relevant one; the finding about maintenance is what carries over, and STEP-4 states it more forcefully in the semaglutide era.
Who sells liraglutide, and for how much
This trial tested Liraglutide 3.0 mg (Saxenda). Across the 734 sellers on this register, 5 publish a standing monthly cash price for compounded liraglutide, from $149 a month, with a median of $160.
⛔ 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.Wadden TA, Hollander P, Klein S, et al.; NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013. PMID: 23812094.
- 2.Novo Nordisk A/S. Comparison of Liraglutide Versus Placebo in Weight Loss Maintenance in Obese Subjects: SCALE - Maintenance (NCT00781937). ClinicalTrials.gov. 2013. https://clinicaltrials.gov/study/NCT00781937
- 3.Rubino D, Abrahamsson N, Davies M, et al.; STEP 4 Investigators. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021. PMID: 33755728.
- 4.Aronne LJ, Sattar N, Horn DB, et al.; SURMOUNT-4 Investigators. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024. PMID: 38078870.
- 5.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.
- 6.Rubino DM, Greenway FL, Khalid U, et al.; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022. PMID: 35015037.
- 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.