Original Article

Propensity Score Matching to Determine the Impact of Metformin on All-Cause Mortality in Older Veterans with Diabetes Mellitus

Authors: Juliana Ferri-Guerra, MD, Raquel Aparicio-Ugarriza, PhD, Y. Nadeem Mohammed, MD, Otoniel Ysea, MD, Hermes Florez, MD, Jorge G. Ruiz, MD

Abstract

Objectives: To determine whether metformin is associated with reduced all-cause mortality in older adults with diabetes mellitus as compared with insulin or sulfonylureas, and to evaluate whether the metformin cumulative exposure followed a dose-response relation.

Methods: Retrospective cohort study with propensity score matching inveterans 65 years old and older with diabetes mellitus. Patients who had new prescriptions for metformin were matched for demographic and clinical factors with patients receiving new prescriptions for insulin or sulfonylureas using propensity score matching. All-cause mortality risks were compared between metformin and insulin/sulfonylureas using multivariate Cox regression models. A similar approach was used for tertilesof cumulative metformin doses.

Results: A sample of 174 veterans taking metformin was matched with 174 who took insulin/sulfonylureas. Most patients were men (97.4%), White (80.45%),andtheirmean±standarddeviationagewas69.15±7.65years. Metformin exposure was associated with reduced risk of all-cause mortality (hazard ratio 0.57, 95% confidence interval 0.39–0.84, P = 0.005). The upper tertile of cumulative metformin exposure was associated with lower all-cause mortality in the fully adjusted model (hazard ratio 0.28, 95% confidence interval 0.10–0.77, P = 0.013).

Conclusions: This propensity matching study shows that metformin exposure is associated with a lower risk of all-cause mortality. Higher metformin cumulative exposure seems to reduce the risk of all-cause mortality in older veterans with diabetes mellitus.
Posted in: Endocrinology, Diabetes, and Metabolism30

This content is limited to qualifying members.

Existing members, please login first.

If you have an existing account please login now to access this article or view your purchase options.

Purchase only this article ($15)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Centers for Disease Control and Prevention. National diabetes statistics report. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2020
 
2. Sinclair A, Morley JE, Rodriguez-Manas L, et al. Diabetes mellitus in older people: position statement on behalf of the International Association of Gerontology and Geriatrics (IAGG), the European Diabetes Working Party for Older People (EDWPOP), and the International Task Force of Experts in Diabetes. J Am Med Dir Assoc 2012;13:497–502.
 
3. Huang ES, Laiteerapong N, Liu JY, J, et al. Rates of complications and mortality in older patients with diabetes mellitus: the diabetes and aging study. JAMA Intern Med 2014;174:251–258.
 
4. Kalyani RR, Egan JM. Diabetes and altered glucose metabolism with aging. Endocrinol Metab Clin North Am 2013;42:333–347.
 
5. Park SW, Goodpaster BH, Strotmeyer ES, et al. Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes Care 2007;30:1507–1512.
 
6. Morley JE, Malmstrom TK, Rodriguez-Manas L, et al. Frailty, sarcopenia and diabetes. J Am Med Dir Assoc 2014;15:853–859.
 
7. Garcia-Esquinas E, Graciani A, Guallar-Castillon P, et al. Diabetes and risk of frailty and its potential mechanisms: a prospective cohort study of older adults. J Am Med Dir Assoc 2015;16:748–754.
 
8. Abdelhafiz AH, Koay L, Sinclair AJ. The effect of frailty should be considered in the management plan of older people with type 2 diabetes. Future Sci OA 2016;2:FSO102.
 
9. Sinclair AJ, Rodriguez-Manas L. Diabetes and frailty: two converging conditions? Can J Diabetes 2016;40:77–83.
 
10. Schellenberg ES, Dryden DM, Vandermeer B, et al. Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2013;159:543–551.
 
11. Jong CB, Chen KY, Hsieh MY, et al. Metformin was associated with lower all-cause mortality in type 2 diabetes with acute coronary syndrome: a nationwide registry with propensity score-matched analysis. Int J Cardiol 2019;291:152–157.
 
12. LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society* clinical practice guideline. J Clin Endocrinol Metab 2019;104:1520–1574.
 
13. Barzilai N, Crandall JP, Kritchevsky SB, et al. Metformin as a tool to target aging. Cell Metab 2016;23:1060–1065.
 
14. Piskovatska V, Stefanyshyn N, Storey KB, et al. Metformin as a geroprotector: experimental and clinical evidence. Biogerontology 2019;20:33–48.
 
15. Han Y, Xie H, Liu Y, et al. Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis. Cardiovasc Diabetol 2019;18:96.
 
16. Qaseem A, Humphrey LL, Sweet DE, et al. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2012;156:218–231.
 
17. Roumie CL, Hung AM, Greevy RA, et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann Intern Med 2012;157:601–610.
 
18. Campbell JM, Bellman SM, Stephenson MD, et al. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: a systematic review and meta-analysis. Ageing Res Rev 2017;40:31–44.
 
19. Bannister CA, Holden SE, Jenkins-Jones S, et al. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, nondiabetic controls. Diabetes Obes Metab 2014;16:1165–1173. .
 
20. Phadnis MA, Shireman TI, Wetmore JB, et al. Estimation of drug effectiveness by modeling three time-dependent covariates: an application to data on cardioprotective medications in the chronic dialysis population. Stat Biopharm Res 2014;6:229–240.
 
21. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983;70:41–55.
 
22. Cho J, Copeland LA, Stock EM, et al. Protective and risk factors for 5-year survival in the oldest veterans: data from the Veterans Health Administration. J Am Geriatr Soc 2016;64:1250–1257.
 
23. Orkaby AR, Nussbaum L, Ho YL, et al. The burden of frailty Among U.S. veterans and its association with mortality, 2002-2012. J Gerontol A Biol Sci Med Sci 2019;74:1257–1264.
 
24. Wang CP, Lorenzo C, Espinoza SE. Frailty attenuates the impact of metformin on reducing mortality in older adults with type 2 diabetes. J Endocrinol Diabetes Obes 2014;2(2).
 
25. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci 2007;62:722–727.
 
26. Sohn MW, Arnold N, Maynard C, et al. Accuracy and completeness of mortality data in the Department of Veterans Affairs. Popul Health Metr 2006;4:2.
 
27. Williamson E, Morley R, Lucas A, et al. Propensity scores: from naive enthusiasm to intuitive understanding. Stat Methods Med Res 2012;21:273–293.