Clinical outcomes of basal insulin and oral antidiabetic agents as an add-on to dual therapy in patients with type 2 diabetes mellitus

Abstract

While basal insulin remains the most effective antidiabetic agent and substantially reduces the risk of hypoglycemia, few studies have examined the comparative effect of basal insulin in the real-world setting. this study aimed to assess the outcomes of adding basal insulin compared with thiazolidinediones (TZDs) or dipeptidyl peptidase-4 inhibitors (DPP-4is) as a third antidiabetic agent in patients with type 2 diabetes mellitus (T2DM). A retrospective cohort study involving T2DM was conducted with health administrative data in Taiwan. Patients starting a third antidiabetic agent after receiving a metformin-containing dual combination were identified. The study endpoints included composite major adverse cardiovascular events (MACEs), all-cause mortality, and hypoglycemia. Propensity score matching and Cox modeling were used for analysis. After matching, the basal insulin and TZD groups contained 6,101 and 11,823 patients, respectively, and the basal insulin and DPP-4i groups contained 6,051 and 11,900 patients, respectively. TZDs and DPP-4is were both associated with similar risks of MACEs and hypoglycemia but a lower risk of all-cause mortality than basal insulin (TZDs: HR 0.55, 95% CI 0.38-0.81; DPP-4is: HR 0.56, 95% CI 0.39-0.82). Further studies are needed to elucidate the findings of increased all-cause mortality risk in patients receiving basal insulin, especially those with advanced diabetes.Diabetes mellitus (DM) substantially increases the risk of cardiovascular diseases (CVDs) and associated deaths; therefore, intensive glucose control has long been considered a gold standard to reduce the occurrence of CVDs 1 . The 10-year follow-up study of the UKPDS (UK Prospective Diabetes Study) revealed a beneficial long-term effect of early intensive glucose control on the reduction in macrovascular events 2 , although this effect did not appear in other clinical trials with advanced DM populations and relatively short follow-up periods 3-5 . Insulin is regarded as the most effective antidiabetic agent for glycemic control, and it possesses a better ability in the preservation of β-cell function than oral hypoglycemic agents (OHAs) 6-8 . The emergence of long-acting basal insulin ameliorates the problem of insulin-associated hypoglycemia 9 . However, the initiation of insulin therapy is often delayed in clinical practice because most patients are reluctant to or inconvenienced by using injectable medications 10 .The role of basal insulin as an add-on antidiabetic agent remains unclear [11][12][13] . Previous studies have shown that the combination of metformin and sulfonylureas dominated in dual therapy in the early phase of disease management [14][15][16][17] , and other OHAs, such as thiazolidinediones (TZDs) and dipeptidyl peptidase-4 inhibitors (DPP-4is), are common treatment options after the failure of dual therapy 11,13,16 . Several observational studies compared insulin to OHAs and noted a significantly increased risk of CVDs or all-cause mortality associated with insulin 18-23 . However, most of these s...

Long-term HbA1c variability and the development and progression of diabetic retinopathy in subjects with type 2 diabetes

“…Insulin is effective in glycemic control and it possesses a better ability in the preservation of β-cell function, however, it has a risk of hypoglycemia 30 . It is reported that insulin use was associated with an increased risk of all-cause mortality compared to the use of dipeptidyl peptidase-4 inhibitors or thiazolidinediones 31 , 32 . This study was not originally designed to evaluate the influence of medications on DR development and detailed information such as dosage or duration of drug use was not included.…”

Relationship between the early initiation of insulin treatment and diabetic complications in patients newly diagnosed with type 2 diabetes mellitus in Korea: A nationwide cohort study

“…Cheng et al found an increased risk of all-cause mortality when they compared patients initiating DPP-4 inhibitors or TZD with those initiating basal insulin as an additional third agent after dual OAD combination therapy 17 . The lack of association between insulin use and all-cause mortality in the present study might be explained by the fact that our study was based on the first prescription after type 2 diabetes mellitus diagnosis.…”

Injektionstherapie (GLP1-Rezeptor Agonisten und Insulin) bei Typ 2 Diabetes mellitus (Update 2023)

“…Einzelstudien und Meta-Analysen konnten zeigen, dass die Kombination von Insulin mit oralen Antidiabetika bei Menschen mit Typ 2 Diabetes zu einer bis zu 40 %igen Einsparung des Insulinbedarfs gegenüber der alleinigen Insulintherapie führt [ 26 , 27 ]. Zur Reduktion der Insulinresistenz und wegen der günstigen Gewichtseffekte wird ein Beibehalten von Metformin bei jeder Form der Insulintherapie bei Typ 2 Diabetes empfohlen [ 28 ].…”