Aim: To compare the efficacy and safety of a glucagon-like peptide-1 receptor agonist (GLP1RA) plus basal insulin versus basal-bolus insulin treatment in patients with very uncontrolled type 2 diabetes. Materials and methods:The SIMPLE study was a 6-month pragmatic, randomized, open-label trial testing the effectiveness of two approaches to treat patients with type 2 diabetes and HbA1c ≥10%. We randomized patients to detemir plus liraglutide or detemir plus aspart (before each meal). The primary endpoint was change in HbA1c; changes in body weight, insulin dose, hypoglycaemia and diabetes-related quality-of-life were secondary outcomes.Results: We randomized 120 participants aged 47.4 ± 9.5 years, Hispanic 40%, African American 42%, diabetes duration 10 [25th-75th percentile (6 to 15)] years, body mass index 37.2 ± 10.3 kg/m 2 . HbA1c decreased more with GLP1RA plus basal insulin [12.2% (95% CI 11.8% to 12.6%) to 8.1% (95% CI 7.4% to 8.7%)] compared with basal-bolus insulin [11.8% (95% CI 11.5% to 12.2%) to 8.8% (95% CI 88.1% to 9.55%)]; estimated treatment difference (ETD) of −1.1% (95% CI −2.0% to −0.1%) (non-inferiority margin 0.4% and P = .0001, superiority P = .026). Compared with basal-bolus insulin, treatment with GLP1RA plus basal insulin led to a body weight ETD of −3.7 kg (95% CI −5.8 to −1.5; P = .001), fewer patients experiencing hypoglycaemia [66.1% vs 35.2% (P = .002)], and greater improvements in general/current health perception, treatment satisfaction, and fear of hypoglycaemia, while taking a lower total daily dose of insulin [estimated treatment ratio 0.68 (95% CI 0.55 to 0.84)].Conclusions: In patients with HbA1c ≥10% treatment with GLP1RA plus basal insulin, compared with basal-bolus insulin, resulted in better glycaemic control and body weight, lower insulin dosage and hypoglycaemia, and improved quality of life. This treatment strategy is an effective and safe alternative to a basal-bolus insulin regimen.

Basal-bolus insulin (BBI) is the most established treatment strategy for patients with very elevated HbA1c (>10%), especially if symptomatic. The combination of metformin (Met), GLP-1 receptor agonist (GLP-1RA) and basal insulin (BI) is a very effective glucose lowering strategy, but it has not been evaluated in patients with very elevated HbA1c. This is the first randomized trial comparing a GLP-1RA+BI treatment regimen to a BBI treatment regimen in patients with very uncontrolled (HbA1c>10%) T2D. Basal insulin detemir was either continued at the prior dose or initiated at 0.3 units/kg and self-titrated. GLP-1RA liraglutide was titrated according to label to 1.8 mg/day. Meal-time insulin aspart was initiated at 0.1 units/kg/meal and self-titrated. Metformin was continued or (re)initiated if tolerated, all other hypoglycemic agents were discontinued. The primary outcome was change in HbA1c at 6 months, analyzed using a mixed model repeated measures analysis. We randomized 120 patients with a mean age (SD) 47.4 (9.5) years, Hispanic 48%, diabetes duration of 10.54 (7.19) years, 76% were already treated with insulin, HbA1c 12.1 (1.4) %, BMI 37.2 (10.3) kg/m2, 86% had one or more symptoms of hyperglycemia. Both treatment strategies lead to dramatic improvements in HbA1c, treatment with GLP-1RA+BI, compared with BBI, resulted in significantly better glycemic control, weight, insulin dosage, and hypoglycemia (Table).Table. Effects of treatment with GLP-1RA + basal insulin (GLP1RA+BI) compared with basal-bolus insulin (BBI) on primary & secondary outcomes.VariableGLP1RA+BI GroupBBI GroupEstimated Treatment DifferenceP value between groupsBaseline6 monthsBaseline6 monthsHbA1c(%)12.2 (11.8 to 12.6)8.1 (7.4 to 8.7)11.8 (11.5 to 12.2)8.8 (6.0 to 9.1)1.1 (0.1 to 2.0)0.03Weight (kg)98.2 (89.7 to 106.6)97.5 (89.1 to 106.0)104.5 (96.2 to 112.8)107.6 (99.3 to 115.9)3.7 (1.53 to 5.9)<0.01TDD Insulin (U/day) (median, 25th to 75th percentile)25.0 (22.0 to 36.0)64.0 (39.5 to 80.0)60.0 (43.0 to 72.0)100.0 (66.0 to 155.0)0.3* (0.1 to 0.5)0.01HbA1c ≤7% N (%)NA20 (44.4)NA9 (20.5)Odds Ratio 0.32 (0.13 to 0.82)0.02Patients with any hypoglycemia (glucose <70 mg/dL) N (%)NA19 (35.2)NA37 (66.1)NA<0.01Data represents Least Squares Means (95% confidence intervals) unless otherwise noted.*ETD for the log transformed value Disclosure M. Abreu: None. A. Tumyan: None. A. Elhassan: None. O. Papacostea: None. K. Peicher: None. P. Dimachkie: None. M.S. Siddiqui: None. B. Adams-Huet: None. X. Li: None. L. Pop: None. I. Lingvay: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, AstraZeneca, Intarcia Therapeutics, Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S, Merck Sharp & Dohme Corp., Pfizer Inc., GI Dynamics Inc., Novartis AG. Other Relationship; Self; Sanofi, AstraZeneca, Boehringer Ingelheim GmbH, Novo Nordisk A/S.

Objective: This study reports an unusual presentation of autoimmune polyglandular syndrome type II (APS-II) with recurrent cardiac tamponade due to pericarditis in a young male patient. Methods: We report clinical presentation, laboratory data, and imaging studies for our patient. Relevant literature is reviewed. Results: Our patient was a 29-year-old Hispanic man with a history of primary hypothyroidism who presented to the emergency department complaining of chest pain and found to have cardiac tamponade due to pericardial effusion. He rapidly became hemodynamically unstable and underwent pericardiocentesis, after which he was admitted to the intensive care unit. The patient gradually recovered and was discharged after 15 days of hospitalization, while the etiology of his illness remained unclear. Four months later, he again presented with similar symptoms and was diagnosed with recurrent cardiac tamponade. He became hemodynamically unstable, and underwent pericardiocentesis. His morning serum cortisol level was found to be undetectable and further workup confirmed autoimmune etiology of primary adrenal insufficiency. The presence of hypothyroidism, vitiligo, and subsequent adrenal insuf-ficiency in the context of positive glutamic acid decarboxylase antibody suggested the diagnosis of APS-II in our patient. Conclusion: APS-II has many associated complications. Cardiac tamponade is a rare presentation of APS-II but it is crucial to recognize it because recurring pericarditis and cardiac tamponade can be fatal in these patients. Accurate diagnosis and timely hormone replacement with monitoring for cardiac complications can prevent fatal outcomes. (AACE Clinical Case Rep. 2017;3:e353-e356) Abbreviations: APS-II = autoimmune polyglandular syndrome type II; ED = emergency department; T1DM = type 1 diabetes mellitus e354 APS-II and Cardiac Tamponade, AACE Clinical Case Rep. 2017;3(No. 4)

The SIMPLE study was a randomized trial comparing two treatment strategies [basal insulin (BI) + GLP-1 RA vs. basal-bolus insulin (BBI)] in patients with T2DM and very elevated HbA1c (>10%). The glucose lowering agents were provided free of charge for the 6-month study. This post-hoc analysis evaluates compliance with the assigned glucose lowering agents, and the effect of compliance on glycemic control. Compliance was assessed by inventory of the returned medication. Optimal compliance was defined as >80% use of the respective agent over the entire duration of the study. Mixed model repeated measures analysis with compliance as a covariate was used to evaluate the treatment effect on HbA1c. The 120 randomized patients had a mean (SD) age 47.4 (9.5) years, BMI 37.2 (10.3) kg/m2, and baseline HbA1c 12.1 (1.4)%. The proportion of patients with optimal compliance with basal insulin was numerically higher in the BI+GLP-1 RA vs. BBI group (p=0.16); optimal compliance with GLP-1 RA was higher compared to bolus insulin (p=0.04) (Table). Compliance was an independent predictor for glycemic improvement (P = 0.008); treatment with BI+GLP-1 RA was superior at lowering HbA1c after adjustment for compliance (P = 0.01). Optimal compliance was low in this patient population. While compliance was a significant contributor to glycemic control, treatment with BI+GLP-1 RA improved HbA1c more than BBI independent of medication compliance.Table. Patients with optimal compliance with glucose lowering agents (>80% over the 6-month study duration) in the two treatment groups (basal insulin + GLP1 RA compared with basal-bolus insulin) and the effect of compliance on glycemic control.Basal-Bolus Insulin Group(BBI, n=56a)Basal Insulin + GLP1 RA Group (BI+GLP1 RA, n=54a)Patients with optimal compliance:Basal Insulin8 (14.3)14 (25.9)Bolus Insulin6 (10.7)NAGLP1 RANA14 (25.9)Change in HbA1c:Adjusted for compliance- 3.1 (-4.0,-2.2)- 4.5 (-5.2,-3.8)Optimal Compliance subgroup-3.2 (-4.8,-1.6)-5.4 (-6.6, -4.2)Low Compliance subgroup-3.0 (-3.7,-2.3)-3.6 (-4.4,-2.8)Data are Least squares means (95%CI) or N (%); NA - Not applicable. acompliance data available for n=110 (intention-to-treat analysis sample). Disclosure A. Elhassan: None. M. Abreu: None. A. Tumyan: None. O. Papacostea: None. K. Peicher: None. P. Dimachkie: None. M.S. Siddiqui: None. B. Adams-Huet: None. X. Li: None. L. Pop: None. I. Lingvay: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, AstraZeneca, Intarcia Therapeutics, Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S, Merck Sharp & Dohme Corp., Pfizer Inc., GI Dynamics Inc., Novartis AG. Other Relationship; Self; Sanofi, AstraZeneca, Boehringer Ingelheim GmbH, Novo Nordisk A/S.