From the Guidelines
The incidence of clinically significant hypoglycemia in users of Wegovy (semaglutide) is very low when used as indicated, with minimal risk for hypoglycemia, but may increase when combined with insulin or sulfonylureas. Hypoglycemia is not commonly reported as a significant adverse effect with Wegovy when used alone, as GLP-1 receptor agonists, such as semaglutide, stimulate insulin secretion and reduce glucagon secretion in a glucose-dependent manner 1. However, the risk increases substantially when Wegovy is combined with insulin or insulin secretagogues (like sulfonylureas). Some key points to consider include:
- The effect of semaglutide on glucose-lowering efficacy is greatest among GLP-1 receptor agonists, with minimal risk for hypoglycemia 1
- When combined with insulin or sulfonylureas, the risk of hypoglycemia depends on the concurrent medications, with rates of clinically significant hypoglycemia ranging from approximately 1-6%
- Patients should be educated about recognizing hypoglycemia symptoms (shakiness, sweating, confusion, irritability) and instructed to monitor blood glucose more frequently when starting Wegovy, especially if they are on other diabetes medications
- Dose adjustments of insulin or sulfonylureas may be necessary when initiating Wegovy to prevent hypoglycemic episodes.
From the FDA Drug Label
Table 2. Hypoglycemia Adverse Reactions in Placebo-Controlled Trials in Patients with Type 2 Diabetes Mellitus Placebo OZEMPIC 0. 5 mg OZEMPIC 1 mg Monotherapy (30 weeks) N=129 N=127 N=130 Severe† 0% 0% 0% Documented symptomatic (≤70 mg/dL glucose threshold) 0% 1.6% 3.8% Severe† or Blood Glucose Confirmed Symptomatic (≤56 mg/dL glucose threshold) 1.6% 0% 0% Add-on to Basal Insulin with or without Metformin (30 weeks) N=132 N=132 N=131 Severe† 0% 0% 1.5% Documented symptomatic (≤70 mg/dL glucose threshold) 15.2% 16.7% 29. 8% Severe† or Blood Glucose Confirmed Symptomatic (≤56 mg/dL glucose threshold) 5.3% 8.3% 10.7%
The incidence of clinically significant hypoglycemia in users of Wegovy (semaglutide) is not directly stated in the provided drug labels. However, the labels do provide information on the incidence of hypoglycemia adverse reactions in placebo-controlled trials.
- Severe hypoglycemia occurred in 0% to 1.5% of patients.
- Documented symptomatic hypoglycemia (≤70 mg/dL glucose threshold) occurred in 0% to 29.8% of patients.
- Severe or blood glucose confirmed symptomatic hypoglycemia (≤56 mg/dL glucose threshold) occurred in 0% to 10.7% of patients. It is essential to note that these values are based on trials with OZEMPIC, which is another brand name for semaglutide, and may not directly apply to Wegovy. Additionally, the provided information does not specifically address the incidence of clinically significant hypoglycemia in users of Wegovy. Therefore, no conclusion can be drawn regarding the exact incidence of clinically significant hypoglycemia in Wegovy users based on the given data 2, 2, 2.
From the Research
Incidence of Clinically Significant Hypoglycemia in Users of Wegovy (Semaglutide)
- The incidence of clinically significant hypoglycemia in users of Wegovy (semaglutide) is reported in several studies, including the SUSTAIN 4 trial 3 and the SUSTAIN FORTE trial 4.
- In the SUSTAIN 4 trial, severe or blood glucose-confirmed hypoglycemia was reported by 16 (4%) participants with 0.5 mg semaglutide and 20 (6%) with 1.0 mg semaglutide, compared to 38 (11%) with insulin glargine 3.
- In the SUSTAIN FORTE trial, the incidence of severe hypoglycemia was not specifically reported, but the trial found that semaglutide 2.0 mg was superior to 1.0 mg in reducing HbA1c, with additional bodyweight loss and a similar safety profile 4.
- Another study reported that unintentional semaglutide overdoses did not result in hypoglycemia, suggesting that the risk of hypoglycemia with semaglutide may be low 5.
- However, it is worth noting that the risk of hypoglycemia may be increased when semaglutide is combined with other medications, such as sulfonylureas 6.
Comparison to Other Treatments
- The incidence of clinically significant hypoglycemia with semaglutide is generally lower compared to other treatments, such as insulin glargine 3.
- A study comparing the incidence of hypoglycemia in patients with type 2 diabetes found that the risk of non-severe hypoglycemia was higher with sulfonylureas and insulin, but not with incretin-based therapy, which includes semaglutide 6.