Umbrella review quantifies GLP-1 drugs as insulin adjuncts in type 1 diabetes

A new umbrella review published in Diabetes, Obesity and Metabolism on September 10, 2026, pooled data from 18 prior systematic reviews covering 56 unique studies to ask whether GLP-1 receptor agonist drugs help people with type 1 diabetes when added to their insulin regimen ^[1][2]. The researchers searched PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and OpenAlex from inception through June 22, 2026, and included 35 randomized controlled trials and 21 nonrandomized studies ^[1][2].

The team found a large amount of overlap among the earlier reviews, mostly because so many of them relied on the same two liraglutide trials, called ADJUNCT ONE and ADJUNCT TWO. Using a measure called corrected covered area, the overlap came out to 19.6%, which the authors call very high ^[1][2]. To correct for this, they reanalyzed the original study data themselves rather than simply combining prior reviews' results ^[1][2].

After reanalysis, adding a GLP-1 drug to insulin therapy reduced average blood sugar levels, measured by HbA1c, by 0.23 percentage points, with moderate certainty in the evidence ^[1][2]. Body weight dropped by an average of 3.93 kilograms, also with moderate certainty ^[1][2]. Daily insulin dose fell by 5.74 units per day, though this finding had lower certainty ^[1][2]. Time in range, a measure of how much of the day blood sugar stays in a healthy zone, did not improve significantly, and the evidence for this outcome was rated very low certainty ^[1][2].

On safety, the review found no statistically significant increase in severe low blood sugar episodes or diabetic ketoacidosis, though both estimates carried low certainty and wide confidence intervals, meaning the true effect remains uncertain ^[1][2]. Gastrointestinal side effects were clearer: nausea occurred nearly three times as often, vomiting occurred about three times as often, and people were roughly twice as likely to stop treatment because of side effects, all with high certainty ^[1][2]. Diarrhea was reported more often but the increase was not statistically significant ^[1][2].

Why it matters for patients

GLP-1 drugs like semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) are approved in the United States for type 2 diabetes or obesity, not type 1 diabetes. This review looked at using GLP-1 drugs as an add-on to insulin in type 1 diabetes, a use the study authors describe as not routine ^[1][2]. For someone with type 1 diabetes already on insulin, the findings suggest a possible weight and insulin-dose benefit, but the HbA1c improvement was small and time in range, a marker many patients and doctors track closely, did not clearly improve ^[1][2].

The higher rates of nausea, vomiting, and treatment discontinuation are also relevant because they mirror side effects widely reported with these drugs in other conditions. The authors note that diabetic ketoacidosis and severe hypoglycemia risks remain uncertain rather than ruled out, since the confidence intervals for those outcomes were wide ^[1][2]. The study's authors conclude that the evidence does not support routine use of GLP-1 drugs in type 1 diabetes, but say there may be a role for select patients where weight loss and lower insulin needs are a priority ^[1][2].

Because so much of the underlying evidence traces back to just two older liraglutide trials, the certainty behind several outcomes is limited, and the authors flag this heavy reliance on a small evidence base as a key limitation of the field so far ^[1][2]. What is not addressed in this review is how newer GLP-1 drugs, dosing schedules, or longer-term outcomes might change this picture; those questions are not yet answered by the available data ^[1][2].