Pooled analysis supports adding tirzepatide to basal insulin in type 2 diabetes

A pooled analysis of two phase 3 trials found that adding tirzepatide to titrated basal insulin lowered A1c, fasting blood sugar and daily insulin dose across every patient subgroup examined, with low rates of clinically significant low blood sugar ^[1].

The analysis combined data from 1,072 participants in SURPASS-5 and SURPASS-6 who took tirzepatide as an add-on to basal insulin glargine ^[1]. Tirzepatide is sold as Mounjaro for type 2 diabetes and Zepbound for weight management. In SURPASS-5, tirzepatide was compared with placebo; in SURPASS-6, it was compared with insulin lispro, a rapid-acting mealtime insulin. In both trials, the basal insulin was titrated toward a target dose ^[1].

The researchers divided participants four ways: by starting A1c (at or below 8.5% versus above 8.5%), by age (under 65 versus 65 and older), by how long they had type 2 diabetes (under 10 years versus 10 or more years), and by daily insulin glargine dose (under 50 international units versus 50 or more) ^[1].

At the primary endpoint, tirzepatide added to basal insulin was linked to significant reductions in A1c, fasting serum glucose and insulin glargine dose in all of those subgroups, with P values below 0.001. There was no significant heterogeneity between subgroups — meaning the effect did not vary much depending on which group a patient fell into — with all interaction P values above 0.1 ^[1].

Low blood sugar was the main safety question. The paper reports that clinically significant hypoglycemia was uncommon, and that the highest incidence rates appeared in younger participants who started with an A1c above 8.5% and had had type 2 diabetes for 10 years or more ^[1]. The authors concluded that the combination was associated with lower A1c and lower insulin doses with a low incidence of hypoglycemia regardless of baseline age, A1c, diabetes duration or basal insulin dose ^[1].

Some specifics are not in the published abstract. The exact average changes in A1c, fasting glucose, insulin dose and body weight appear in figures rather than in the abstract text, so the size of the average drops has not been spelled out there ^[1]. The analysis was exploratory and performed after the two trials ended, rather than planned in advance, so it is generally treated as a look that can generate hypotheses rather than proof of how any one patient will respond ^[1].

Several authors report financial ties to the companies involved. Three are employees and shareholders of Eli Lilly, which makes tirzepatide; another is an employee and shareholder of Pfizer and a shareholder of Eli Lilly, and was an employee of Eli Lilly when the manuscript was developed; two others report consulting honoraria or trial fees paid to their institutions by Eli Lilly, Novo Nordisk, Pfizer and other companies ^[1].

Why it matters for patients

For people with type 2 diabetes who take long-acting insulin and still run above their A1c goal, doctors often consider adding another medicine. This analysis suggests that age, how long someone has had diabetes, how high their A1c started and how much insulin they take did not change the direction of the result ^[1].

Low blood sugar is the main concern when diabetes treatment is intensified. The study reports low overall rates, but also points to younger patients with a higher starting A1c and a longer history of diabetes as the group with the highest rates. That is a broad pattern from pooled trial data, not a prediction for any individual ^[1].

The analysis does not compare tirzepatide head-to-head with other add-on options, does not report long-term outcomes such as heart or kidney effects, and does not cover cost or insurance coverage; none of that is included ^[1]. Whether adding tirzepatide works better or worse than adding a GLP-1 medicine such as semaglutide has not been reported here ^[1].

What happens next

The two underlying trials are registered at ClinicalTrials.gov as NCT04039503 (SURPASS-5) and NCT04537923 (SURPASS-6) ^[1]. Whether these pooled results will lead to any change in tirzepatide's prescribing information, or to new trials, has not been disclosed ^[1].