Abstract
Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice. The long-acting GLP-1RA, semaglutide, is available for once-weekly injection and in a new once-daily oral formulation. Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e.g., patients with hepatic impairment or renal impairment). The oral formulation represents a useful option to help improve acceptance and adherence compared with injectable formulations for patients with a preference for oral therapy, and may lead to earlier and broader use of GLP-1RAs in the T2D treatment trajectory. Oral semaglutide should be taken on an empty stomach, which may influence the choice of formulation. As with most GLP-1RAs, initial dose escalation of semaglutide is required for both formulations to mitigate gastrointestinal adverse events. There are also specific dose instructions to follow with oral semaglutide to ensure sufficient gastric absorption. The evidence base surrounding the clinical use of semaglutide is being further expanded with trials investigating effects on diabetic retinopathy, cardiovascular outcomes, and on the common T2D comorbidities of obesity, chronic kidney disease, and non-alcoholic steatohepatitis. These will provide further information about whether the benefits of semaglutide extend to these other indications.
Highlights
For patients with type 2 diabetes (T2D), early control of hyperglycemia after diagnosis is important to prevent debilitating long-term complications and to reduce diabetes-related mortality [1, 2]
Like all other GLP-1RAs, semaglutide is not recommended in patients with end-stage renal disease (ESRD) [25, 26]
The benefits of GLP-1RAs are becoming increasingly recognized in international T2D recommendations and, along with other agents targeted at T2D pathophysiology, such as sodiumglucose co-transporter-2 inhibitor (SGLT2i), their initiation early in the disease trajectory is advocated
Summary
For patients with type 2 diabetes (T2D), early control of hyperglycemia after diagnosis is important to prevent debilitating long-term complications and to reduce diabetes-related mortality [1, 2]. As reviewed by Meier in this supplement [32], in head-to-head trials with other long-acting GLP-1RAs, subcutaneous semaglutide 1.0 mg produced superior HbA1c and weight reductions compared with exenatide ER 2.0 mg (estimated treatment difference [ETD] –0.62% and 3.78 kg; both p < 0.0001, respectively) [33] and with dulaglutide 1.5 mg (ETD – 0.41% and 3.55 kg; both p < 0.0001, respectively) [34].
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