Efficacy of Semaglutide Injection in the Treatment of Type 2 Diabetes Mellitus and its Impact on C-Peptide Levels

Abstract

Type 2 Diabetes Mellitus (T2DM) remains a significant global health challenge, necessitating more effective therapeutic strategies. This study was to observe the impact of semaglutide on the C-Peptide levels and glycemic variability. This retrospective evaluation was conducted from January 2020 to January 2023 at our hospital, involving 172 patients diagnosed with T2DM. Patients were stratified into two groups: the observation group (86 patients) received semaglutide injections plus metformin, and the control group (86 patients) received only metformin. Treatment efficacy was assessed using changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h BG), and C-Peptide levels. Additional evaluations included changes in glycemic variability indicators such as standard deviation of blood glucose (SDBG), mean of daily differences (MODD), and mean amplitude of glycemic excursions (MAGE). The observation group showed significantly greater improvements in glycemic control and C-Peptide levels compared to the control group. Specifically, the observation group achieved a significant reduction in HbA1c from 70 mmol/mol to 53 mmol/mol, FBG from 10.91 mmol/l to 6.12 mmol/l, and increased C-Peptide levels in both fasting and postprandial states. Improvements in glycemic variability were also more pronounced in the observation group. There was no significant difference in the incidence of adverse events between the two groups. Semaglutide combined with metformin significantly enhances the efficacy of treatment in T2DM patients, with marked improvements in C-Peptide levels, glycemic control, and reduction in glycemic variability. This combination therapy not only offers superior glucose management but also appears to bolster pancreatic function.

Keywords

type 2 diabetes mellitus - semaglutide - C-peptide - glycemic control - glycemic variability

Publication History

Received: 24 February 2025

Accepted after revision: 17 May 2025

Article published online:
05 June 2025

• References

• 1 Ahmad E, Lim S, Lamptey R. et al. Type 2 diabetes. Lancet 2022; 400: 1803-1820
• 2 Tinajero MG, Malik VS. An update on the epidemiology of type 2 diabetes: a global perspective. Endocrinol Metab Clin North Am 2021; 50: 337-355
• 3 Magliano DJ, Sacre JW, Harding JL. et al. Young-onset type 2 diabetes mellitus - implications for morbidity and mortality. Nat Rev Endocrinol 2020; 16: 321-331
• 4 Mehdi SF, Pusapati S, Anwar MS. et al. Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent. Front Immunol 2023; 14: 1148209
• 5 Nolen-Doerr E, Stockman MC, Rizo I. Mechanism of glucagon-like peptide 1 improvements in type 2 diabetes mellitus and obesity. Curr Obes Rep 2019; 8: 284-291
• 6 Frías JP, Davies MJ, Rosenstock J. et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 2021; 385: 503-515
• 7 Andreadis P, Karagiannis T, Malandris K. et al. Semaglutide for type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab 2018; 20: 2255-2263
• 8 Goldenberg RM, Steen O. Semaglutide: review and place in therapy for adults with type 2 diabetes. Can J Diabetes 2019; 43: 136-145
• 9 Davies M, Pieber TR, Hartoft-Nielsen ML. et al. Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: a randomized clinical trial. JAMA 2017; 318: 1460-1470
• 10 Li A, Su X, Hu S. et al. Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract 2023; 198: 110605
• 11 Wysham C, Shubrook J. Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications. Postgrad Med 2020; 132: 676-686
• 12 Yan W, Bai R, Yan M. et al. Preoperative fasting plasma C-peptide levels as predictors of remission of type 2 diabetes mellitus after bariatric surgery: a systematic review and meta-analysis. J Invest Surg 2017; 30: 383-393
• 13 Wang Y, Wan H, Chen Y. et al. Association of C-peptide with diabetic vascular complications in type 2 diabetes. Diabetes Metab 2020; 46: 33-40
• 14 Gibbons C, Blundell J, Tetens Hoff S. et al. Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes. Diabetes Obes Metab 2021; 23: 581-588
• 15 Zinman B, Aroda VR, Buse JB. et al. Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes:tThe PIONEER 8 trial. Diabetes Care 2019; 42: 2262-2271
• 16 Blüher M, Rosenstock J, Hoefler J. et al. Dose-response effects on HbA(1c) and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia 2024; 67: 470-482
• 17 Zaazouee MS, Hamdallah A, Helmy SK. et al. Semaglutide for the treatment of type 2 diabetes mellitus: a systematic review and network meta-analysis of safety and efficacy outcomes. Diabetes Metab Syndr 2022; 16: 102511
• 18 Shaman AM, Bain SC, Bakris GL. et al. Effect of the glucagon-like peptide-1 receptor agonists semaglutide and liraglutide on kidney outcomes in patients with type 2 diabetes: pooled analysis of SUSTAIN 6 and LEADER. Circulation 2022; 145: 575-585
• 19 Yin DG, Ding LL, Zhou HR. et al. Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials. Endocr J 2021; 68: 739-742
• 20 Clements JN, Isaacs D, Hartman RE. et al. Pharmacokinetics and clinical implications of oral semaglutide for type 2 diabetes mellitus. Clin Pharmacokinet 2021; 60: 153-163
• 21 Ramos-Leví AM, Matía P, Cabrerizo L. et al. C-peptide levels predict type 2 diabetes remission after bariatric surgery. Nutr Hosp 2013; 28: 1599-1603
• 22 Saisho Y. Postprandial C-peptide to glucose ratio as a marker of  cell function: implication for the management of type 2 diabetes. Int J Mol Sci 2016; 17: 744
• 23 Christensen MB, Gæde P, Hommel E. et al. Glycaemic variability and hypoglycaemia are associated with C-peptide levels in insulin-treated type 2 diabetes. Diabetes Metab 2020; 46: 61-65
• 24 Yang Q, Liu Y, Peng J. et al. High levels of serum C-peptide are associated with a decreased risk for incident renal progression in patients with type 2 diabetes: a retrospective cohort study. BMJ Open Diabetes Res Care 2023; 11: e003201
• 25 Granhall C, Donsmark M, Blicher TM. et al. Safety and pharmacokinetics of single and multiple ascending doses of the novel oral human GLP-1 analogue, oral semaglutide, in healthy subjects and subjects with type 2 diabetes. Clin Pharmacokinet 2019; 58: 781-791
• 26 Ishibashi C, Kozawa J, Hosakawa Y. et al. Pancreatic fat is related to the longitudinal decrease in the increment of C-peptide in glucagon stimulation test in type 2 diabetes patients. J Diabetes Investig 2020; 11: 80-87
• 27 Takahashi Y, Nomoto H, Yokoyama H. et al. Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: a multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study). Diabetes Obes Metab 2023; 25: 1503-1511
• 28 Perreault L, Davies M, Frias JP. et al. Changes in glucose metabolism and glycemic status with once-weekly subcutaneous semaglutide 2.4 mg among participants with prediabetes in the STEP program. Diabetes Care 2022; 45: 2396-2405