Discussion
This prospective randomized clinical trial compared glycemic control, clinical outcome and frequency of hypoglycemic events in elderly patients with T2D treated with basal insulin and OADs in LTC facilities. Most of the patients enrolled in our study were admitted to LTC facilities for subacute rehabilitation. We observed that both treatment regimens resulted in a rapid and sustained improvement in glycemic control without significant differences between patients treated with basal insulin or with OADs. In addition, we observed no differences in the frequency of hypoglycemia, length of stay, need for ER visit, hospital admission or mortality between treatment groups.
Few prospective randomized studies have reported on the safety and efficacy of different treatment strategies in elderly patients with diabetes admitted to LTC facilities. In general, recommendations for the management of diabetes in this population are extrapolated from studies in the hospital setting or from ambulatory patients with diabetes.15 ,20–24 Most nursing home residents with T2D are managed with insulin and/or oral antidiabetic agents,12 ,25 ,26 with basal insulin being recommended as the first-line therapy,27 ,28 and OAD agents usually considered to be less safe and effective than insulin therapy. In contrast to previous beliefs, our results indicate no significant differences in efficacy and safety of insulin and OAD treatment in elderly nursing home patients with type 2 diabetes.
A major finding in our study is that treatment with a low dose of basal insulin and OAD resulted in a similar frequency of hypoglycemia, with ∼30% of patients in both groups. A higher but non-significant proportion of patients receiving sulfonylureas alone or in combination with other agents (34%) develop hypoglycemia compared to participants not exposed to sulfonylureas (28%). Previous studies have highlighted the importance of avoiding hypoglycemia in the elderly, as it may be associated with increased risk of complications and mortality.6 ,29–32 Data from the National Health and Nutrition Examination Survey (NHANES) gathered from 2001 through 2010 suggest that a large proportion of older adults with diabetes are potentially overtreated. Of the older adults with an HbA1C level of less than 7%, more than half were treated with either insulin or sulfonylurea, agents that may lead to severe hypoglycemia.33 In a recent observational study in 1409 LTC residents, we reported that 42% of patients had ≥1 episodes of hypoglycemia and patients with hypoglycemia were more likely to require emergency room, hospital transfers and had higher mortality, than patients without hypoglycemia.6 In agreement with these studies, we found that patients with hypoglycemia experienced more episodes of acute kidney injury and a higher rate of complications compared to patients without hypoglycemia. These results emphasize the need for prevention of hypoglycemia with agents not associated with hypoglycemia in this vulnerable population. In this regard, a multicenter study is currently underway comparing the safety and efficacy of DPP-4 inhibitors and low-dose basal insulin in LTC facilities (NCT02061969).
Our study confirmed the results of previous studies that showed that glycemic control in elderly nursing home residents with diabetes is more often tight than poor.34 ,35 The average HbA1C levels reported in numerous nursing home studies have ranged between 5.9% and 7.5%,35–38 with HbA1C goals achieved in more than three-fourths of nursing home patients.34 ,35 Current guidelines for older residents with diabetes mellitus suggest that HbA1C goals be individualized,24 ,39 ,40 with an HbA1C target of <7.5% in residents with good cognitive and functional status and without significant hypoglycemia.13 A target of 8–8.5% may be appropriate in residents with a history of severe hypoglycemia, limited life expectancy, comorbid conditions and longstanding diabetic complications.27 ,28 In our study, we randomized most patients with persistent fasting and premeal hyperglycemia. It is not known if tailoring therapy guiding for correction of fasting or daily hyperglycemia has the same impact in improving outcome or in reducing the frequency of hypoglycemia compared to a targeted HbA1C level in elderly participants with type 2 diabetes.
The main limitations of our study include its small sample size, and the relatively well-controlled population enrolled in the study based on HbA1C alone. The fact that patients were selected based on their previous regimen, including diet with or without oral agents, likely skewed our sample towards a better-controlled population, which probably does not reflect the overall glycemic control spectrum among all institutionalized patients with diabetes. Our study does suggest, however, that a significant proportion of patients are potentially overtreated in LTC or SAR (>50% were treated with sulfonylureas before enrollment). Another limitation is the relatively shorter length of stay (over a month) of most patients. Given the above limitations, the generalization of our results to all older adults with diabetes, in LTC or SAR facilities, is not possible, as patients treated with insulin or combinations of insulin with oral agents who are potentially more fragile (LTC residents particularly), might be at an even higher risk for hypoglycemia than the patients enrolled in our study. Larger and longer studies are needed to address these additional questions.
In summary, our randomized controlled study indicates that elderly residents with relatively well controlled T2D in LTC facilities and subacute rehabilitation settings can achieve and maintain similar glycemic control, and experience a similar rate of hypoglycemic events, when treated with either a low dose of basal insulin or with oral antidiabetic agents. Further studies that include patients with a wider range of glycemic control, including previous treatment with insulin are needed to further understand different therapeutic regimens, and to develop strategies aimed at preventing hypoglycemia in this vulnerable population.