MD Conference Express ADA 2013 - (Page 13)

creatinine, urinary ratio of albumin to creatinine, use of angiotensin receptor blockers, educational status, presence of integrated health plan, and presence of certified diabetes educator on staff at randomization. Model 2 added assignment to blood pressure or lipid trial, treatment assignment within these, severe hypoglycemia, and weight change. Model 3 added the updated average HbA1C, and Model 4 added the glycemic treatment arm assignment. Results from all 4 models by total, basal, and bolus insulin are presented in Table 1. Table 1. HRs for CV Mortality of Insulin Dose (per 1 unit/kg) From Cox Proportional Hazards Model Unadjusted Insulin HR Categories (95% CI)* Model 1* Model 2* Model 3* Model 4* Total insulin 1.83 (1.45-2.31) p<0.0001 1.21 (0.92-1.6) p=0.1726 1.21 (0.91-1.61) p=0.1912 1.12 (0.84-1.49) p=0.4540 0.99 (0.74-1.34) p=0.9693 Basal insulin 2.29 (1.62-3.23) p<0.0001 1.3 (0.87-1.94) p=0.2073 1.29 (0.85-1.95) p=0.2272 1.13 (0.74-1.72) p=0.5636 0.94 (0.61-1.46) p=0.7955 Bolus insulin 3.36 (2.0-5.66) p<0.0001 1.65 (0.88-3.11) p=0.1172 1.63 (0.85-3.12) p=0.1399 1.48 (0.77-2.84) p=0.2365 1.23 (0.63-2.4) p=0.5478 *For the unadjusted model, and Models 1 to 4, only a single insulin exposure was entered into the model at a time. Thus, each cell represents the results for that insulin variable being the only one within the model. Based on the unadjusted HRs, a daily insulin dose increase by 1 unit/kg of body weight was associated with a 1.83- (total insulin), 2.29- (basal insulin) and 3.36-fold increase in risk of CV mortality (all p<0.0001). However, results from the four models did not confirm these findings. After adjustment for baseline covariates in Model 1, the HRs became nonsignificant indicating no association of insulin dose with CV mortality. Additionally, no association between insulin dose and CV mortality emerged after adjustments were made for on-treatment factors. Dr. Siraj concluded that these results do not support the idea that insulin dose is an independent risk factor for CV mortality in the ACCORD population. Canagliflozin Reduces HbA1C in Patients With Stage 3 CKD, With the Change Greater in Patients With Higher eGFR Written by Wayne Kuznar The sodium glucose cotransporter-2 inhibitor canagliflozin reduces HbA1C level in patients with type 2 diabetes mellitus (T2DM) and stage 3 chronic kidney disease (CKD), an effect that is more pronounced with higher levels of estimated glomerular filtration rate (eGFR), according to the results of a pooled analysis. Gary Meininger, MD, Janssen Research and Development LLC, Raritan, New Jersey, USA, presented the results of this pooled analysis of four randomized, doubleblind, placebo-controlled Phase 3 trials that compared canagliflozin with placebo in patients with inadequately controlled T2DM and stage 3 CKD. Options for glycemic control in patients with T2DM and impaired renal function are limited, said Dr. Meininger. Canagliflozin has been approved in the United States as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. However, its approved dosage is limited to 100 mg QD in patients with moderate renal impairment with an eGFR ≥45 and <60 mL/min/1.73 m2, and it is not indicated in patients with an eGFR <45 mL/min/1.73 m2. The present pooled analysis included 1085 patients with T2DM and stage 3 CKD (eGFR ≥30 and <60 mL/min/1.73 m2) who were randomized to canagliflozin 100 or 300 mg, or placebo for 18 to 26 weeks. In the overall study population, the mean change from baseline to efficacy assessment in HbA1C was -0.52% in the canagliflozin 100-mg group; -0.62% in the canagliflozin 300-mg group; and -0.14% in the placebo group (p<0.001 for both canagliflozin groups vs placebo). When assessed by baseline eGFR, a greater reduction in HbA1C with canagliflozin was observed in patients with eGFR ≥45 mL/min/1.73 m2 and <60 mL/min/1.73 m2 than in those with eGFR ≥30 and <45 mL/min/1.73 m2. In the 88.2% of all participants who were on background insulin or a sulfonylurea, the rates of documented episodes of hypoglycemia were greater with canagliflozin 100 mg and 300 mg (41.9% and 43.8%, respectively) than with placebo (29.2%). Weight loss was also greater in the canagliflozin groups than in the placebo groups, and the effect was greater in patients with eGFR ≥45 mL/min/1.73 m2 than in those with eGFR ≥30 and <45 mL/min/1.73 m2. Systolic blood pressure decreased more in the overall study population in the canagliflozin groups versus the placebo group. In the subgroup with eGFR ≥30 and <45 mL/min/1.73 m 2, systolic blood pressure increased by 0.8 mm Hg in each canagliflozin group and by 5.7 mm Hg in the placebo group. The incidence of overall adverse events (AEs) was higher with canagliflozin (74.0% with 100 mg and 75.3% with 300 mg) than with placebo (70.4%). Intravascular volume-related adverse events were also more common with canagliflozin (5.0% and 8.5% in the 100- and 300mg groups, respectively) than with placebo (2.6%). The percentage of these events in the canagliflozin groups was greater in patients with eGFR ≥30 and <45 mL/min/1.73 m2 (6.6% and 11.1% in the 100- and 300-mg groups, respectively) relative to placebo (1.7%) than in those with eGFR ≥45 mL/min/1.73 m2 (4.2% and 7.1% with 100-mg and 300-mg Official Peer-Reviewed Highlights From the American Diabetes Association 73rd Scientific Sessions 2013 13

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