Aim: To summarize the existing literature concerning the association between polypharmacy and adverse health consequences in elderly patients with type 2 diabetes mellitus.Methods: We searched four literature databases (PubMed/Medline, ScienceDirect and Web of Science) through April 2019. We included all studies that addressed the association between polypharmacy and all-cause of mortality, glycemic control, macrovacular complications, hospitalization, potentially inappropriate medicines, drug-drug interactions and fall. A statistical program OpenMeta [Analyst] was used. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with a random effects model. I2 statistics was performed to assess heterogeneity.Results: Out of sixteen studies, three studies were used for meta-analysis. A statistically significant association was found between polypharmacy and all-cause mortality (OR = 1.622, 95% CI (1.606-1.637) P < 0.001), and myocardial infarction (OR = 1.962, 95% CI (1.942-1.982), P < 0.001. Non-statistically significant association with evidence of moderate heterogeneity was found between polypharmacy and stroke (OR = 1.335; 95% CI (0.532-3.346), P = 0.538, I2 = 45%), and hospitalization (OR = 1.723; 95% CI (0.983-3.021), P = 0.057, I2 = 57%).Conclusions: Pooled risk estimates reveal that polypharmacy is associated with increased all-cause mortality, macrovacular complications and hospitalization using categorical definitions. These findings assert the need for interventions that optimize the balance of benefits and harms in medicines prescribing. [ABSTRACT FROM AUTHOR]