Three-year SCALE data shows liraglutide delays type 2 diabetes
A three-year Lancet trial found 2% of adults with prediabetes on liraglutide 3.0 mg developed type 2 diabetes versus 6% on placebo, but half the participants dropped out before week 160 [1].
Researchers reported 160-week results from the SCALE Obesity and Prediabetes trial in The Lancet, finding that adults with prediabetes who took liraglutide 3.0 mg were less likely to be diagnosed with type 2 diabetes during treatment than those on placebo [1]. The trial was funded by Novo Nordisk [1].
What the trial did
The randomized, double-blind, placebo-controlled study enrolled adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with other weight-related conditions [1]. Participants were assigned 2:1 to once-daily subcutaneous liraglutide 3.0 mg or matching placebo, on top of a reduced-calorie diet and increased physical activity [1]. The study ran between June 1, 2011, and March 2, 2015, across 191 clinical research sites in 27 countries, and is registered as NCT01272219 [1].
In total, 2,254 people were randomly assigned: 1,505 to liraglutide and 749 to placebo [1]. The primary outcome was time to diabetes onset by 160 weeks, roughly three years [1].
The numbers
By week 160, 26 of 1,472 people (2%) in the liraglutide group were diagnosed with diabetes while on treatment, compared with 46 of 738 (6%) in the placebo group [1]. Among those diagnosed, the mean time from randomization to diagnosis was 99 weeks (standard deviation 47) with liraglutide versus 87 weeks (SD 47) with placebo [1].
After accounting for the different diagnosis rates between groups, the investigators calculated that time to diabetes onset over 160 weeks among all randomized participants was 2.7 times longer with liraglutide than placebo (95% CI 1.9 to 3.9, p<0.0001), corresponding to a hazard ratio of 0.21 (95% CI 0.13 to 0.34) [1].
Weight loss also favored the drug. At week 160, average change in body weight was -6.1% (SD 7.3) with liraglutide versus -1.9% (SD 6.3) with placebo, an estimated treatment difference of -4.3% (95% CI -4.9 to -3.7, p<0.0001) [1].
Serious adverse events were reported by 227 of 1,501 randomized and treated people (15%) in the liraglutide group versus 96 of 747 (13%) on placebo [1]. The abstract does not break down what those events were.
The dropout problem
Only 1,128 participants (50%) completed the study through week 160 [1]. Withdrawals totaled 714 people (47%) in the liraglutide group and 412 (55%) in the placebo group [1]. The authors explicitly flag as a limitation that people who withdrew were not followed after they stopped treatment [1]. That means the diabetes counts describe what happened to people still on assigned treatment, not to everyone who started.
The authors' own conclusion is cautious: liraglutide 3.0 mg "might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes" [1].
Why it matters for patients
This is one of the longer placebo-controlled looks at whether a GLP-1 medicine can push back a type 2 diabetes diagnosis in people who have prediabetes and obesity, rather than simply lowering weight or blood sugar over a year [1]. The absolute difference over three years was 4 percentage points — 2% versus 6% [1] — which is a smaller gap than the hazard ratio of 0.21 might suggest on its own.
The high dropout rate is the main reason to read the result carefully. With half the participants gone by week 160 and no follow-up after discontinuation [1], it is not known from this trial what happened to people once they stopped the drug, including whether diabetes risk rebounded. The published abstract also uses the word "delays" language indirectly: the headline finding is longer time to onset while on treatment [1], not proof of permanent prevention.
Also worth noting: liraglutide 3.0 mg is a daily injection [1], different from the weekly semaglutide and tirzepatide products many people use now. This trial says nothing about those newer drugs, and the 160-week data do not address cost, insurance coverage, or how long treatment would need to continue.
What happens next
The Lancet published a linked commentary, "Treating prediabetes in the obese: are GLP-1 analogues the answer?" by Farr and Mantzoros, posted online the same day and appearing in the April 8, 2017 print issue [1]. A correction notice, listed as "Department of Error," was also published in The Lancet on April 8, 2017 [1]; the content of that correction is not described in the available source.
Sources
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