New once-weekly GLP-1 agonist for diabetes

Administered once weekly, Ozempic is indicated for the treatment of type II diabetes inadequately controlled by diet and exercise, either as monotherapy when metformin is contraindicated or not tolerated, or with other hypoglycaemics.

Ozempic is given by subcutaneous injection into the abdomen, thigh or upper arm. It may be administered at any time of day without regard for meals.

Semaglutide vs dulaglutide

Semaglutide was compared with another once-weekly GLP-1 agonist, dulaglutide, in a head-to-head, open-label parallel group study involving 1201 patients with type II diabetes inadequately controlled on metformin monotherapy. The reduction in mean percentage HbA_1c from baseline to week 40 was significantly greater in patients randomised to receive semaglutide 500 microgram than in those who received dulaglutide 750 microgram (-1.5 vs -1.1 percentage points, p<0.0001) and in those receiving semaglutide 1mg than in those receiving dulaglutide 1.5mg (-1.8 vs
-1.4 percentage points, p<0.0001).

Significantly more patients achieved the predefined HbA_1c treatment targets of less than 7% and less than or equal to 6.5% at week 40 with semaglutide than with dulaglutide (p< 0.0001 for the low-dose comparison and p=0.0021 for the high-dose comparison).

In addition, the reduction in mean bodyweight from baseline to week 40 (the secondary endpoint) was significantly greater in patients who
received semaglutide 500 microgram than in those who received dulaglutide 750 microgram (-4.6kg vs -2.3kg, p<0.0001). Similar results were seen for semaglutide 1mg compared with dulaglutide 1.5mg (-6.5kg vs -3.0kg, p<0.0001).

Semaglutide vs sitagliptin

In a double-blind, active-controlled parallel group study in 1231 patients inadequately controlled on metformin and/or glitazones, patients randomised to receive semaglutide 500 microgram or 1mg once weekly had a significantly greater reduction in HbA_1c from baseline to week 56 than those randomised to receive the oral dipeptidyl peptidase 4 inhibitor sitagliptin 100mg once daily (-1.3 and -1.6 percentage points, respectively, vs -0.5 percentage points; p< 0.0001 for both comparisons).

Similarly, significantly greater weight loss was seen in the semaglutide 500 microgram and 1mg groups than in the sitagliptin group (-4.3kg and -6.1kg, respectively, vs -1.9kg; p< 0.0001 for both comparisons).

Semaglutide vs exenatide

In an open-label parallel group study (n=813) comparing semaglutide with another GLP-1 agonist in patients taking one or two oral
hypoglycaemics (metformin and/or a glitazone and/or a sulfonylurea), semaglutide 1mg once weekly was superior to exenatide 2mg once weekly in improving glycaemic control (HbA_1c change from baseline to week 56, -1.5 vs -0.9 percentage points, p<0.0001) and reducing bodyweight (-5.6kg vs -1.9kg, p<0.0001).

In addition, a greater proportion of patients in the semaglutide group achieved HbA_1c targets of less than 7% and less than or equal to 6.5% at week 56 than in the exenatide group (p< 0.0001 for both).

Semaglutide vs insulin glargine

Superiority of semaglutide has also been demonstrated in an open-label parallel group study (n=1089) comparing semaglutide (500 microgram or 1mg weekly) with insulin glargine (starting dose, 10iu once daily) in insulin-naive patients inadequately controlled on metformin alone or with a sulfonylurea. Compared with insulin glargine, semaglutide was associated with greater reductions from baseline to week 30 in HbA_1c (-1.21 and -1.64 percentage points, respectively, vs -0.83 percentage points, p< 0.0001 for both comparisons) and weight (losses of 3.47kg and 5.17kg, respectively, vs a gain of 1.15kg, p< 0.0001 for both comparisons) with fewer hypoglycaemic episodes).

Cardiovascular benefit

Cardiovascular benefits of semaglutide treatment were shown in a two-year cardiovascular outcomes study (n=3297) in which the drug
significantly reduced the risk of cardiovascular events (non-fatal MI, non-fatal stroke and cardiovascular death) compared with placebo when added to standard of care.

The incidence of common adverse effects with semaglutide was similar to that observed with other GLP-1 agonists, the most commonly reported adverse effects being hypoglycaemia and GI upset.