The Efficacy and Safety of Hypoglycemic Agents in the Middle-Aged and Elderly Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis
Abstract
Background: We aimed to evaluate the efficacy and safety of combined hypoglycemic agents and insulin therapy in the middle-aged and elderly patients with diabetes through a meta-analysis.
Methods: Literature was searched in PubMed, Cochrane Library, EMbase, Web of Science, WanFang, VIP, and CNKI databases for studies on the combined use of hypoglycemic agents and insulin therapy in the middle-aged and elderly patients with diabetes, with a search time limit up to February 2023.
Results: This article includes 8 RCTs. The risk of bias assessment shows that one article had a low risk of bias, one article have an unclear risk of bias, and 6 articles have a high risk of bias. The meta-analysis results show that the combination of hypoglycemic agents and insulin has better blood glucose control (P=0.0001); fasting blood glucose reduction is more significant (P<0.00001); the 2-hour postprandial blood glucose reduction is more noticeable (P=0.002); HbA1c reduction is more pronounced (P=0.005); however, there is no difference in the incidence of adverse reactions between the two groups (P=0.09).
Conclusion: The combination of hypoglycemic agents and insulin in the treatment of middle-aged and elderly diabetic patients can reduce the fasting blood glucose, the 2-hour postprandial blood glucose, and HbA1c, and reduce adverse reactions. However, due to the limitations in the number and quality of the included studies, the conclusion still requires further verification from more high-quality RCTs.
2. Holmager TLF, Lophaven SN, Morten-sen LH, et al (2022). Selective migra-tion and mortality by economic status in Lolland-Falster, Denmark, 1992-2018. Sci Rep,12(1):19970.
3. Zolkepli H, Widodo RT, Mahmood S, et al (2022). A Review on the Delivery of Plant-Based Antidiabetic Agents Using Nanocarriers: Current Status and Their Role in Combatting Hyper-glycaemia. Polymers (Basel),14 (15):2991.
4. Qiao J, Zhang Z, Ji S, et al (2022). A dis-tinct role of STING in regulating glu-cose homeostasis through insulin sensi-tivity and insulin secretion. Proc Natl Acad Sci U S A, 119(7):e2101848119.
5. Kashtoh H, Baek KH (2022). Recent Updates on Phytoconstituent Alpha-Glucosidase Inhibitors: An Approach towards the Treatment of Type Two Diabetes. Plants (Basel),11 (20):2722.
6. Zhang P, Chen M, Zhang H, et al (2022). Effectiveness and safety of basal insu-lin therapy in type 2 diabetes mellitus patients with or without metformin observed in a national cohort in China. BMC Endocr Disord, 22(1):26.
7. Alavudeen SS, Khobrani M, Dhanapal CK, et al (2020). Comparative evalua-tion of biphasic insulin with metfor-min and triple oral hypoglycemic agents (OHA) in type 2 diabetes pa-tients. Saudi Pharm J, 28:210-214.
8. Dashora UK, Sibal L, Ashwell SG, et al (2007). Insulin glargine in combination with nateglinide in people with Type 2 diabetes: a randomized placebo-controlled trial. Diabet Med, 24(4):344-349.
9. Janka HU, Plewe G, Busch K (2007). Combination of oral antidiabetic agents with basal insulin versus pre-mixed insulin alone in randomized el-derly patients with type 2 diabetes mellitus. J Am Geriatr Soc, 55(2):182-188.
10. Mu PW, Chen YM, Lu HY, et al (2012). Effects of a combination of oral anti-diabetes drugs with basal insulin thera-py on β-cell function and glycaemic control in patients with newly diag-nosed type 2 diabetes. Diabetes Metab Res Rev, 28(3):236-240.
11. Wang Z, Wang J, Kahkoska AR, et al (2021). Developing Insulin Delivery Devices with Glucose Responsiveness. Trends Pharmacol Sci, 42(1):31-44.
12. CUI JP, WU YX (2015). Efficacy of glargine insulin combined with oral hypoglycemic agents in the treatment of type 2 diabetes mellitus in the elder-ly. China Pharmaceutical Guide, 13(27):95-96. (in Chinese)
13. LIU FP (2016). Efficacy of glargine insu-lin combined with oral hypoglycemic agents in the treatment of type 2 dia-betes mellitus in the elderly. Journal of Huaihai Medicine, 34(2):219-220. (In Chinese)
14. Yilmaz H, Gursoy A, Sahin M, et al (2007). Comparison of insulin mono-therapy and combination therapy with insulin and metformin or insulin and rosiglitazone or insulin and acarbose in type 2 diabetes. Acta Diabetol, 44(4):187-192.
15. Li J, Ji J, Liu F, et al (2019). Insulin Glargine and Acarbose in the treat-ment of elderly patients with diabetes. Pak J Med Sci, 35(3):609-613.
16. Billings LK, Doshi A, Gouet D, et al (2018). Efficacy and Safety of IDegLi-ra Versus Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes Un-controlled on Metformin and Basal In-sulin: The DUAL VII Randomized Clinical Trial. Diabetes Care, 41(5):1009-1016.
17. Chen X (2021). Effect of oral hypogly-cemic drugs combined with glargine in-sulin in the treatment of outpatients with type 2 diabetes mellitus. China Prac Med, 16:117-119.
18. Papa G, Fedele V, Chiavetta A, et al (2008). Therapeutic options for elderly diabetic subjects: open label, random-ized clinical trial of insulin glargine added to oral antidiabetic drugs versus increased dosage of oral antidiabetic drugs. Acta Diabetol, 45(1):53-59.
19. Zinman B, Aroda VR, Buse JB, et al (2019). Efficacy, Safety, and Tolera-bility of Oral Semaglutide Versus Pla-cebo Added to Insulin With or With-out Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Diabetes Care,42(12):2262-2271.
20. Yang Q, Lang Y, Yang W, et al (2023). Efficacy and safety of drugs for people with type 2 diabetes mellitus and chronic kidney disease on kidney and cardiovascular outcomes: a systematic review and network meta-analysis of randomized controlled trials. Diabetes Res Clin Pract, 198:110592.
21. Xu X, Xu W, Zhuo Q, et al (2022). The efficacy and safety of dapagliflozin combined with oral hypoglycemic agents in patients with type 2 diabetes: a systematic review and meta-analysis. Ann Palliat Med, 11(3):1028-1037.
| Files | ||
| Issue | Vol 54 No 7 (2025) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v54i7.19114 | |
| Keywords | ||
| Hypoglycemic agents Insulin Middle-aged and elderly Diabetes mellitus | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |



