No abstract

Islet autoantibodies are typically associated with type 1 diabetes, but have been found in patients diagnosed with type 2 diabetes in whom they are associated with lower adiposity. The significance of autoantibody positivity in overweight and obese patients is not well understood. The aim of this study was to determine the prevalence and clinical significance of islet autoantibodies in overweight/obese adults diagnosed with type 2 diabetes. This study includes 204 participants at one site of the multicenter Look AHEAD (Action for Health in Diabetes) trial (ClinicalTrials.gov identifier: NCT00017953) which randomized overweight/obese adults diagnosed with type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. We measured antibodies to glutamic acid decarboxylase, insulinoma antigen-2, and zinc transporter 8. Participants with and without autoantibodies were compared with respect to baseline clinical features, and longitudinal changes in weight, hemoglobin A1c, and antihyperglycemic medications. We found that 13 participants (6.4%) were autoantibody positive, including six of 47 participants (12.8%) with BMI ≥40 kg/m2. At baseline, autoantibody positive participants had higher HDL cholesterol (1.27 vs. 1.09 mmol/L, P=0.034) and lower fasting C-peptide (0.32 vs. 0.57 nmol/L, P=0.049). Over four years, autoantibody positive participants lost 5.1 kg more weight than autoantibody negative participants (P=0.056). Longitudinal changes in hemoglobin A1c did not differ by autoantibody status, though autoantibody positive participants were more likely to increase the number of antihyperglycemic medications or initiate insulin (P=0.011). In conclusion, islet autoantibodies were present in 6.4% of overweight/obese adults with type 2 diabetes including those with severe obesity, and were associated with distinct clinical features. The effect of autoantibody positivity on weight loss interventions requires further study.

Background Clinical guidelines recommend that metformin be continued after insulin is initiated among patients with type 2 diabetes, yet little is known regarding how often metformin or other non-insulin diabetes medications are continued in this setting. Methods We conducted a retrospective cohort study to characterize rates and use patterns of six classes of non-insulin diabetes medications: biguanides (metformin), sulfonylureas, thiazolidinediones (TZDs), glucagon-like peptide 1 receptor agonists (GLP1 receptor agonists), dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors), and sodium-glucose co-transporter inhibitors (SGLT2 inhibitors), among patients with type 2 diabetes initiating insulin. We used the 2010–2015 MarketScan Commercial Claims and Encounters data examining 72,971 patients with type 2 diabetes aged 18–65 years old who initiated insulin and had filled a prescription for a non-insulin diabetes medication in the 90 days prior to insulin initiation. Our primary outcome was the proportion of patients refilling the various non-insulin diabetes medications during the first 90 days after insulin initiation. We also used time-to-event analysis to characterize the time to discontinuation of specific medication classes. Results Metformin was the most common non-insulin medication used prior to insulin initiation (N = 53,017, 72.7%), followed by sulfonylureas (N = 25,439, 34.9%) and DPP4 inhibitors (N = 8,540, 11.7%). More than four out of five patients (N = 65,902, 84.7%) refilled prescriptions for any non-insulin diabetes medications within 90 days after insulin initiation. Within that period, metformin remained the most common medication with the highest continuation rate of 84.6%, followed by SGLT2 inhibitors (81.9%) and TZDs (79.3%). Sulfonylureas were the least likely medications to be continued (73.6% continuation) though they remained the second most common medication class used after insulin initiation. The median time to discontinuation varied by therapeutic class from the longest time to discontinuation of 26.4 months among metformin users to the shortest (3.0 months) among SGLT2 inhibitor users. Conclusion While metformin was commonly continued among commercially insured adults starting insulin, rates of continuation of other non-insulin diabetes medications were also high. Further studies are needed to determine the comparative effectiveness and safety of continuing insulin secretagogues and newer diabetes medications after insulin initiation.