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The Impact of Polypharmacy in Elderly Patients with Type 2 Diabetes 

Nov 3, 2020
Editor: Steve Freed, R.PH., CDE

Author: Nour Salhab, Pharm.D. Candidate, USF College of Pharmacy

Can the use of polypharmacy put elderly patients at increased risk for hospitalization, falls, and all-cause mortality? 

Polypharmacy can be associated with many adverse effects, especially when it comes to elderly, frail patients. Risk of hypoglycemia, medication adherence, drug-drug interactions, worsened quality of life, increased risk of hospitalization, mortality rate, and health care costs are all associated with polypharmacy. However, there are no available data that examines all patient outcomes when it comes to polypharmacy. This article wanted to summarize the existing literature discussing polypharmacy and different adverse health outcomes in elderly patients with type 2 diabetes.  


This article served as a systematic review and meta-analysis. They examined observational studies, including cross-sectional studies, cohort studies, case series, case-control studies, and Interventional studies, which included randomized controlled trials and quasi-experimental studies. Only articles that were written in English were included in the analysis. The characteristics of patients were 65 years of age or older with a diagnosis of type 2 diabetes. Primary outcomes included all-cause mortality, glycemic control (Functionally independent (HbA1c 7.0-7.5%), subcategory (A) frail (HbA1c ≤ 8.5%). (B) Functionally dependent (HbA1c 7.0-8.0%), sub-category (B) dementia (HbA1c ≤ 8.5%)), macrovascular complications (coronary artery disease, heart failure, cerebrovascular disease, and stroke), hospitalization or hospital re-admission. Secondary outcomes included the association between polypharmacy and inappropriate medicines, drug-drug interactions, and falls or fall risk. The odds ratio was used to associate polypharmacy with adverse health consequences. Meta-analysis was used when two or more studies with the same design identified the same outcome using the random-effect model. Heterogeneity was assessed by I2 test.  

After searching the electronic databases and applying the exclusion criteria, 16 studies were included in the systematic review, and three studies were included in the meta-analysis. 1,205,821 patients were included in this review. About 50% of these patients were female, and 97% were elderly. The definition of polypharmacy included using five or more medications in 50% of the studies, and the prevalence was between 6.25 to 93.4%. This review found that almost 28% of elderly patients with type 2 diabetes had an HbA1c of 8% to ≥ 8.5%, even though they were heavily treated with antidiabetic medications. According to the studies, there was no association between HbA1c and polypharmacy use. Using BEER’s criteria, the prevalence of potentially inappropriate medicines was between 22.7% to 79%. Using STOPP criteria, the majority was 48%. The most common medications used were metformin in patients 85 years old or older, benzodiazepines, tricyclic antidepressants, aspirin, non-steroidal anti-inflammatory drugs, and beta-blockers. A Drug-drug interaction associated with polypharmacy was between sulfonylureas and co-trimoxazole antibiotics, causing severe hypoglycemia. Other interactions included oral hypoglycemic agents with hydrochlorothiazide, furosemide, angiotensin-converting enzyme inhibitors, simvastatin, and prednisone. No association between fall or fall risk in polypharmacy was detected. Polypharmacy was significantly associated with all-cause mortality in 2 cohorts (pooled OR, 1.622; 95% CI 1.606 to 1.637, P<0.001, I²=0%). However, when the cross-sectional study was included, it was no longer statistically significant, I²=92%. The association between myocardial infarction and polypharmacy was substantial in 2 cohorts (pooled OR, 1.962; 95% CI 1.942 to 1.982, P<0.001, I²=0%) and remained significant after including the cross-sectional study, I²=94%. There was no significant association between polypharmacy and hospitalization, I²=57%.  

The results of this analysis were mixed. Some studies were able to associate polypharmacy with adverse outcomes, while others could not. Limitations of this meta-analysis included the limitations of the studies that it assessed. One limitation consists of the variable definition of polypharmacy. Another limitation was the representation of the elderly population in clinical trials. Polypharmacy can lead to inappropriate medication use that would increase the risk of adverse health outcomes in elderly patients with type 2 diabetes. Therefore, it should be limited and monitoring parameters established, such as laboratory testing and patient education, to monitor these adverse events.   

Practice Pearls:  

  • Polypharmacy was significantly associated with myocardial infarction but wasnt associated with hospitalization, fall, or fall risk.  
  • A definite association was not established between all-cause mortality and the use of polypharmacy.  
  • Polypharmacy use should be limited regardless of association to optimize medication use in patients at increased risk for adverse health consequences.   


Al-Musawe, Labib, et al. The Association Between Polypharmacy and Adverse Health Consequences in Elderly Type 2 Diabetes Mellitus Patients; a Systematic Review and Meta-Analysis. Diabetes Research and Clinical Practice, 2020 


Nour Salhab, Pharm.D. Candidate, USF College of Pharmacy