medwireNews: The coadministration of cagrilintide and semaglutide produces “clinically relevant improvements” in glycemic control in people with type 2 diabetes who have a BMI of 27 kg/m2 or higher, a team of international researchers report.
The coadministration of both drugs, referred to as CagriSema, resulted in a 2.2 percentage-point reduction in glycated hemoglobin (HbA1c) after 32 weeks of treatment, from an average 8.5% (70 mmol/mol) at baseline.
This reduction was significantly greater than the 0.9 percentage-point decrease from an average 8.1% (65 mmol/mol) seen with cagrilintide alone, but not when compared with the 1.8 percentage-point reduction from an average 8.6% (70 mmol/mol) seen with semaglutide alone.
“Our phase 2 clinical trial is the first study to report efficacy and safety data for treatment with the combination of a GLP-1 receptor agonist and an amlylin analogue in participants with type 2 diabetes,” Juan Frias (Velocity Clinical Research, Los Angeles, California, USA) and colleagues say in The Lancet.
They report that several continuous glucose monitoring parameters were improved from baseline to end of treatment with CagriSema. These included fasting plasma glucose where an average reduction of 3.3 mmol/L from a baseline value of 10.0 mmol/L (180 mg/dL) was seen. The corresponding values for semaglutide and cagrilintide given separately were –2.5 mmol/L and –1.7 mmol/L, from average baseline values of 9.8 and 8.9 mmol/L (177 and 160 mg/dL), respectively.
CagriSema also achieved a greater improvement in the time spent within the blood glucose target range of 3.9–10.0 mmol/L (70–180 mg/dL) than either agent given alone. This increased from an average of 45.9% at baseline to 88.9% at week 32 with CagriSema, from 32.6% to 76.2% with semaglutide, and from 56.9% to 71.7% with cagrilintide.
And, consistent with a prior phase 1b trial in people with overweight or obesity, CagriSema was associated with a significantly greater 15.6% weight loss at week 35, from an average 104.3 kg at baseline, when compared with both semaglutide (–5.1% from 105.4 kg) and cagrilintide alone (–8.1% from 107.4 kg).
“These data support further investigation of CagriSema in this population in longer and larger phase 3 studies,” suggest Frias and team, who also reported the data at the 83rd ADA Scientific Sessions in San Diego, California, USA.
In all, 92 patients (78% White, 64% men) with a mean age of 58 years were included in the study and randomly allocated to receive weekly subcutaneous injections of CagriSema (n=31), cagrilintide alone (n=30), or semaglutide alone (n=31). Both cagrilintide and semaglutide were started at doses of 0.25 mg to 0.50 mg and escalated until a maintenance dose of 2.4 mg was reached at 16 weeks. The patients then received 2.4 mg of their allocated treatments for a further 16 weeks.
Discussing the findings in a related commentary, Caroline Apovian and Marie McDonnell, both from Brigham and Women’s Hospital in Boston, Massachusetts, USA, note: “The HbA1c reduction and weight loss in patients with obesity and type 2 diabetes rival the efficacy of semaglutide and tirzepatide, albeit in a phase 2 trial.”
They observe that the weight loss achieved with CagriSema might even surpass these two drugs in people with obesity alone, perhaps equaling that of bariatric surgery.
There also appears to be a synergistic effect on both glycated hemoglobin and weight loss when the two drugs are used together, the commentators point out.
There are of course “some caveats” beyond this being a phase 2 study, caution Apovian and McDonnel. Notably, the baseline duration of diabetes was shorter in the CagriSema group (6.4 years) than in the semaglutide (9.2 years) and cagrilintide (10.7 years) groups, which may have skewed the findings in favor of the combination due to preserved beta-cell function.
Nevertheless, “CagriSema is the next in a series of gut hormone analogues with the potential to herald in a new era in treating obesity and preventing diabesity,” they suggest.
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Lancet 2023; doi: 10.1016/S0140-6736(23)01163-7
Lancet 2023; doi: 10.1016/S0140-6736(23)01291-6