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This month's highlights

Dr Jim McMorran BM BCh PhD DCH DRCOG MRCGP FRCGP

A recent paper in the New England Journal of Medicine presents the 176-week data from the SURMOUNT-1 randomised controlled trial, which involved a double-blinded intervention with tirzepatide (at one of three doses) or placebo.

All participants received lifestyle intervention, which included regular counselling sessions with a dietitian or qualified health professional that focused on healthy eating with a 500-kcal daily deficit and 150 minutes or more of physical activity per week.

This new publication reports on key secondary endpoints for the subset of trial participants who had both obesity and prediabetes at baseline (n=1032). Data from a 17-week off-treatment safety follow-up period are also presented.

At 176 weeks, the mean change in body weight among the participants who received tirzepatide was −12.3% (5-mg dosage), −18.7% (10-mg dosage) and −19.7% (15-mg dosage), while in the placebo group it was −1.3% (P<0.001 for all comparisons versus placebo). In addition, a significantly lower proportion of participants received a diagnosis of type 2 diabetes in the tirzepatide group (pooled across dosages) than in the placebo arm (1.3% versus 13.3%; P<0.001).

These data are impressive. But also of great interest is what happened during the 17-week safety follow-up period, when trial participants were no longer taking tirzepatide or placebo.

After 17 weeks off treatment, the proportions of participants who had developed type 2 diabetes had reached 2.4% in the tirzepatide group and 13.7% in the placebo group. In other words, by the end of those 17 weeks, type 2 diabetes was noted to have developed in an additional 1.1% of the tirzepatide group, which means that the number of cases among participants who received tirzepatide for the 176 weeks of the trial had nearly doubled.

In terms of change in body mass, an estimated mean regain of 7% was observed over the 17-week off-treatment period. This is undoubtedly a clinically significant level of weight rebound.

The authors state that: “The maintenance of weight reduction and durability of glycemic benefit began to dissipate during the off-treatment follow-up period, which was seen in other trials […] and was therefore expected.”

The authors also note that “these findings support the concept that to maintain weight reduction and glycemic improvements, therapies would need to be continued long-term.”

As clinicians, we need to be aware of factors like these when making prescribing decisions.

For more information then see GPnotebook.

Other highlights in this month’s email include statin use in liver disease, an updated hand, foot and mouth disease section, and a summary of immune checkpoint inhibitors side effects.

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