Meta-Analysis on the Efficacy of Novel Glucose-Lowering Agents in Older Patients with Type 2 Diabetes Mellitus

In the United States, approximately 25% of adults aged ≥65 years have type 2 diabetes mellitus (T2DM). 1 CDC. National diabetes statistics report | Diabetes. Available at: https://www.cdc.gov/diabetes/data/statistics-report/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fdiabetes%2Fdata%2Fstatistics%2Fstatistics-report.html. Accessed on July 28, 2022. Google Scholar Patients with T2DM have a 4-fold to 5-fold higher risk of developing cardiovascular (CV) disease, and this risk increases with age. 2 Cigolle CT Blaum CS Halter JB. Diabetes and cardiovascular disease prevention in older adults. Clin Geriatr Med. 2009; 25: 607-641 Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar Additional burden of co-morbidities, frailty, and decreased functional status poses an even higher risk of developing CV disease among older patients. 3 Halter JB Musi N McFarland Horne F Crandall JP Goldberg A Harkless L Hazzard WR Huang ES Kirkman MS Plutzky J Schmader KE Zieman S High KP Diabetes and cardiovascular disease in older adults: current status and future directions. Diabetes. 2014; 63 (August): 2578-2589 Crossref PubMed Scopus (172) Google Scholar Treatment for T2DM in the patients aged >60 years is focused on achieving adequate glycemic control, without inducing hypoglycemia in these patients. Oral hypoglycemic medications, such as metformin, sulfonylureas, and thiazolidinediones, are frequently prescribed for patients with diabetes. However, the effectiveness of these medications is constrained by their side effects, 4 Chentli F Azzoug S Mahgoun S. Diabetes mellitus in elderly. Indian J Endocrinol Metab. 2015; 19: 744-752 Crossref PubMed Scopus (78) Google Scholar especially in older adults. Although it is unclear which of the many conceivable connections between T2DM and morbidity and mortality are more prevalent than the others, multiple plausible pathways have been proposed. 5 American College of Cardiology. Diabetes management in older adults with cardiovascular disease. Available at: https://www.acc.org/latest-in-cardiology/articles/2018/02/28/12/19/diabetes-management-in-older-adults-with-cvd. Accessed on July 29, 2022. Google Scholar Although evidence from recent clinical trials on patients with T2DM shows that novel glucose-lowering agents, such as sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 (GLP-1) agonists, and dipeptidyl peptidase-4 inhibitors (DPP-4is), can decrease all-cause mortality, CV outcomes, and hospitalizations for heart failure (HHFs) in patients with T2DM, older adults are largely under-represented in these clinical trials evaluating medications in T2DM. 6 Marso SP Daniels GH Brown-Frandsen K Kristensen P Mann JF Nauck MA Nissen SE Pocock S Poulter NR Ravn LS Steinberg WM Stockner M Zinman B Bergenstal RM Buse JB LEADER Steering Committee, LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375: 311-322 Crossref PubMed Scopus (4513) Google Scholar ,7 Empagliflozin SS. cardiovascular outcomes, and mortality in type 2 diabetes. Z Gefassmed. 2016; 13: 17-18 Google Scholar Hence, the effectiveness of these drugs in this patient population is not well established.