From the Guidelines
Oral semaglutide is not currently available in India, but its effectiveness in reducing cardiovascular risk has been established in global clinical trials, such as the PIONEER 6 trial, which demonstrated noninferiority to placebo for the primary composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.79 [95% CI 0.57–1.11]; P < 0.001 for noninferiority) 1. The oral formulation of semaglutide has been assessed in the PIONEER 6 trial, a pre-approval trial designed to rule out an unacceptable increase in cardiovascular risk, and the results showed that oral semaglutide was noninferior to placebo for the primary composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.79 [95% CI 0.57–1.11]; P < 0.001 for noninferiority) 1. Some key points to consider:
- The PIONEER 6 trial was a moderate-sized trial that followed 3,183 patients with type 2 diabetes and high cardiovascular risk for a median of 15.9 months 1.
- The trial demonstrated that oral semaglutide was effective in reducing cardiovascular risk, with a hazard ratio of 0.79 (95% CI 0.57–1.11) for the primary composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke 1.
- The effectiveness of injectable semaglutide in Indian populations appears comparable to global clinical trial results, showing significant benefits for blood glucose control and weight reduction 1.
- If oral semaglutide becomes available in India, it may be a viable option for patients with type 2 diabetes who are at high risk of cardiovascular events, but currently, other oral antidiabetic medications like metformin, DPP-4 inhibitors, or SGLT-2 inhibitors may be considered as alternatives 1.
From the Research
Effectiveness of Oral Semaglutide in India
- The effectiveness of oral semaglutide in India can be inferred from studies that have evaluated its efficacy and safety in patients with type 2 diabetes mellitus (T2DM) [ 2 ].
- A comprehensive review of literature found that oral semaglutide 14 mg was superior to placebo or active comparators (empagliflozin, sitagliptin, and liraglutide) in reducing HbA1c and body weight [ 2 ].
- Although no separate data exists for Indians due to the low number of participants, efficacy was similar in Asians [ 2 ].
Efficacy and Safety of Oral Semaglutide
- Oral semaglutide has been shown to be effective in reducing HbA1c and body weight in patients with T2DM, with a significant reduction in HbA1c (MD, -1.30% [95%CI: -1.44, -1.16], P < 0.05) and body weight (MD, -3.17 kg [95%CI: -3.89, -2.45], P < 0.05) compared to placebo [ 3 ].
- Oral semaglutide was also found to be non-inferior to subcutaneous semaglutide and superior to placebo and other GLP-1 RA comparators in reducing HbA1c and body weight [ 3 ].
- The safety profile of oral semaglutide is comparable to other members of its class, with gastrointestinal intolerance being the most commonly observed side effect [ 4 ].
Real-World Studies and Cardiovascular Outcomes
- Real-world studies have demonstrated the effectiveness of oral semaglutide in patients with T2DM and chronic kidney disease (CKD), with significant reductions in HbA1c and body weight [ 5 ].
- Oral semaglutide has also been shown to have a favorable cardiovascular safety profile, with a reduction in cardiovascular and all-cause mortality observed in a randomized controlled trial [ 6 ].