Initial Sulfonylurea Use and Subsequent Insulin Therapy in Older Subjects with Type 2 Diabetes Mellitus

Abstract

BackgroundIn type 2 diabetes mellitus (T2DM), progressive loss of beta cell function over time requires treatment intensification and eventually initiation of insulin for many patients. Relative to metformin, a greater rate of decline in beta cell function over time has been observed with sulfonylurea treatment. The present study examined the association between initial monotherapy with metformin or sulfonylurea and subsequent initiation of insulin in older subjects with T2DM.MethodsIn a retrospective cohort study using the GE electronic medical record database, eligible subjects with T2DM included those ≥65 years who received their first prescription of sulfonylurea or metformin as initial monotherapy between January 1, 2003 to December 31, 2008. The follow-up period lasted to the end of 2009 or the subject’s latest data available. Insulin initiation was determined by prescription records. Logistic regression analysis evaluated the likelihood of insulin addition. A Cox regression model estimated time to initiation of insulin. Differences in baseline characteristics were controlled for using propensity score matching.ResultsOverall, 12,036 subjects were included in the analysis. Mean age was 75 years and 50% were male. Subjects who initiated with sulfonylurea had a significantly (P < 0.001) higher incidence of insulin addition (2.8% vs. 1.4%) compared to those initiated with metformin within 1 year of follow-up. The likelihood of initiating insulin was higher in subjects initiated with sulfonylurea than with metformin (adjusted odds ratio 1.82, 95% confidence interval [CI] 1.40–2.38; P < 0.001). Sulfonylurea use was also significantly associated with a shorter time to insulin use compared to metformin (adjusted hazards ratio 2.10, 95% CI 1.83–2.39; P < 0.001).ConclusionIn a cohort of older subjects with T2DM initiating antihyperglycemic therapy, new users of sulfonylurea monotherapy were more likely to receive insulin therapy and received it earlier than those starting with metformin.

Progression to insulin therapy among patients with type 2 diabetes treated with sitagliptin or sulphonylurea plus metformin dual therapy

“…Results were in line with previous literature that found that patients treated with sulphonylureas had a higher likelihood of insulin use, and earlier insulin initiation, compared with patients treated with other OADs such as metformin [4][5][6][7]14,16]. Only one previous study has assessed the risk of insulin initiation among patients treated with DPP-4 inhibitors specifically, reporting similar findings.…”

“…The finding that HbA1c was significantly associated with insulin initiation is not surprising and is consistent with a number of previous studies 2, 8, 9, 10, 11, 12, 13, 14, 15. After controlling for treatment type, patient characteristics and laboratory assessments, the only significant comorbid condition associated with earlier insulin use was obesity.…”

“…As well as the type of OAD prescribed, the previous literature has described other factors associated with insulin initiation. These include patient demographics, such as younger age [8][9][10][11][12][13], lower income [13] and non-Hispanic race/ethnicity [9], as well as higher glycated haemoglobin (HbA1c) [8][9][10][11][12][13][14][15], fasting plasma glucose [11], serum creatinine [14], duration of T2DM [9,13] and presence of comorbidities and diabetesrelated complications, including depression, lipid disorders, micro-and macrovascular complications and overall chronic disease score [4,7,9,11,13]. Patients who are treated with higher doses of OADs [16], initiate with more than one agent [13], have greater concomitant medication use [11,16], and who have a history of hospitalization are also at increased risk [16].…”

Progression to insulin for patients with diabetes mellitus on dual oral antidiabetic therapy using the US Department of Defense Database

“…Our results were similar, showing 23% of patients placed on insulin within 5 years. Previous studies found that patients started on Met saw a delay in the progression to insulin compared with patients started on SU [7][8][9][10][11][12]. The study in British Columbia found that patients on Met who used SU as second-line therapy were 2.6 times more likely to be initiated on insulin than those placed on TZD as second-line therapy (3.57 vs. 1.37 events per 100 patient-years) [13].…”

Gene expression signature: a powerful approach for drug discovery in diabetes

“…• Increase glucose disposal via activating PPAR-γ to improve insulin signalling in liver, adipose tissue and skeletal muscles , Miyazaki et al 2001, 2003, Kim et al 2002 • Risk of weight gain, congestive heart failure and fractures (Gegick & Altheimer 2004) Sulphonylureas • Directly increase insulin secretion via closing potassium-ATP channel (SUR-1 subunit) on betacells (Proks et al 2002) • Only effective during initial stages of the disease when functional beta-cells are present (Hemmingsen et al 2014) • Fail to provide adequate glycaemic control over the long term (Fu et al 2012) GLP-1 analogues and Gliptins (dipeptidyl peptidase-4 (DPP-4) inhibitors)…”