The short answer
Adding liraglutide helped adults taking basal insulin lose more weight. Insulin was adjusted throughout.
Who took part?
Researchers randomized 396 adults with overweight or obesity and type 2 diabetes to daily liraglutide 3 mg or placebo for 56 weeks. Both groups received intensive behavioral support.
Percent of starting weight; both groups received behavioral support
Original visual based on the study.
| Group or measure | Result |
|---|---|
| Liraglutide 3 mg daily | 5.8% |
| Placebo | 1.5% |
What happened?
Average weight loss was 5.8% with liraglutide versus 1.5% with placebo. About 52% versus 24% lost at least 5% of their starting weight.
Blood-sugar control also improved more with liraglutide. Average insulin doses increased in both groups, but the increase was smaller with liraglutide: roughly 3 versus 18 units daily.
What were the trade-offs?
Digestive side effects affected about 62% versus 47%. Around 72% in each group experienced low blood sugar; severe episodes occurred in both groups.
These results came with glucose monitoring and clinician-directed medication adjustments. They do not establish what happens if someone simply adds liraglutide to unchanged insulin.
Most participants completed follow-up; missing measurements were estimated. The study does not represent people with type 1 diabetes.
Novo Nordisk sponsored the trial and participated in its design, analysis and reporting.
An earlier insulin-combination study
A small 2012 Chinese study compared adding liraglutide with increasing insulin in adults with type 2 diabetes and abdominal obesity. Ninety people entered; the reported results cover 84 completers, 42 in each group.
After 12 weeks, average weight fell 5.62 kg with the liraglutide strategy and rose 2 kg with insulin intensification. Blood-sugar improvements were not statistically different between groups.
This was a comparison of treatment strategies: clinicians also adjusted insulin and other diabetes medicines. The weight difference cannot be attributed to liraglutide alone.
Minor low-blood-sugar episodes were reported by 11.9% versus 31.0%, but overall adverse events were more common with liraglutide: 57.1% versus 33.3%, especially digestive symptoms. Severe hypoglycemia affected no liraglutide participants and two comparison participants.
The short, unblinded study excluded six entrants from the reported results. It does not establish long-term outcomes or a rule for adjusting insulin. Chinese national research grants supported it; the authors declared no conflicts.
A fixed-combination diabetes treatment
DUAL II China studied a different approach: insulin degludec and liraglutide combined in one injection. It randomized 453 adults whose type 2 diabetes was not adequately controlled on basal insulin and metformin.
At 26 weeks, estimated weight change was a 0.7 kg loss with the combination versus a 0.4 kg gain with degludec alone. Blood-sugar control also improved more with the combination. This was a modest weight difference in a diabetes trial, not a test of liraglutide’s 3 mg weight-management dose.
The combination produced fewer confirmed or severe low-blood-sugar episodes, but more digestive adverse events. Two people in each group stopped treatment because of adverse events.
Both groups had an insulin-dose ceiling, which limits comparison with unrestricted insulin adjustment. Missing measurements were handled by carrying the latest recorded value forward. Almost 95% completed the trial.
Novo Nordisk funded the study and writing support; several authors were company employees or shareholders. Read the study.
Sources
Pei and colleagues, Diabetes, Obesity and Metabolism, 2021 (PMID 34387411)
Li and colleagues, Cardiovascular Diabetology, 2012 (PMID 23153177)