Efficacy and Safety of Canagliflozin in Type 2 Diabetes Patients of Different Ethnicity.

OBJECTIVE: To assess the efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin in patients of different ethnicities. DESIGN SETTING AND PATIENTS: Post hoc analysis of data pooled from four randomized, placebo-controlled, phase 3 studies of adults with inadequately controlled type 2 diabetes mellitus (T2DM). INTERVENTIONS: Once daily oral canagliflozin 100 mg or 300 mg, or placebo. MAIN OUTCOME MEASURES: Efficacy endpoints included change from baseline in HbA1c, body weight (BW), systolic blood pressure (SBP), and lipids at week 26; safety and tolerability were assessed by adverse event reports. RESULTS: Of the 2,313 patients included in this pooled analysis, 609 self-identified as Hispanic/Latino. Hispanic/Latino patients had a mean age of 54 years, mean duration of T2DM of 7 years, mean HbA1c of 8.1%, mean body mass index of 31.2 kg/m(2), and mean SBP of 126.1 mm Hg. There were more women in the non-Hispanic/Latino cohort (63%) compared with the Hispanic/Latino cohort. Placebo-subtracted changes in HbA1c were -.82% with canagliflozin 100 mg and -.94% with canagliflozin 300 mg in the Hispanic/Latino cohort, which were similar to reductions observed in the non-Hispanic/Latino cohort. Significantly greater dose-related reductions in HbA1c, BW, and SBP were observed with both canagliflozin doses compared with placebo. Canagliflozin was generally well-tolerated. Genital mycotic infections were less frequent in Hispanic/Latino women than in non-Hispanic/Latino women. CONCLUSIONS: The SGLT2 inhibitor canagliflozin was generally well-tolerated and was associated with clinically meaningful reductions in HbA1c, BW, and SBP in both Hispanic/Latino and non-Hispanic/Latino patients with T2DM.

Oral anti-CD3 monoclonal antibody delays diabetes in non-obese diabetic (NOD) mice: effects on pregnancy and offspring--a preliminary report.

BACKGROUND: The objective was to observe the effect of oral anti-CD3 monoclonal antibody (mAb) on non-obese diabetic mice, pregnancy, and offspring. METHODS: Three protocols are classified as: (1) Twenty non-obese diabetic/ShiLtJ female mice were monitored for type 1 diabetes mellitus. If the blood glucose level was ≥ 250 mg/dL, the mice were treated for 8 days with either 50 or 100 µg oral anti-CD3 monoclonal antibody. If the diabetes resolved, the mice were bred. (2) F1 offspring were monitored for diabetes; 15 female mice became diabetic. Non-diabetic F1 female mice were divided into two groups [ten antibody (Ab) and ten control (C)] and bred. Ab female mice were given 100 µg monoclonal antibody before diabetes development and during pregnancy for 6 weeks. (3) Twenty-five F2 Ab and 23 F2 C mice were monitored. At 15-17 weeks, Ab mice, both female and male, were given 100 µg monoclonal antibody for 8 weeks. RESULTS: (1) The diabetes in four female mice treated with 50 µg did not resolve; in three of the six diabetic female mice treated with 100 µg, the diabetes resolved and the mice were bred. The remaining ten non-diabetic female mice were given 100 µg oral monoclonal antibody and then bred. No diabetes developed during pregnancy; 13 litters were born. (2) Three diabetic Ab female mice sustained their pregnancies versus one diabetic C female mouse (p ≤ 0.05). (3) At 30 weeks, six Ab female and three Ab male mice and seven C female and three C male mice developed diabetes. The number of diabetic Ab and C mice was not different; diagnosis age was significantly different-Ab 23.3 ± 5.1 and C 18.8 ± 3.7 weeks (p ≤ 0.05). CONCLUSIONS: In female non-obese diabetic mice, oral anti-CD3 monoclonal antibody was effective in reversing diabetes and allowing pregnancy and extending longevity, but it did not prevent diabetes in the offspring.

Reductions in Mean 24-Hour Ambulatory Blood Pressure After 6-Week Treatment With Canagliflozin in Patients With Type 2 Diabetes Mellitus and Hypertension.

This randomized, double-blind, placebo-controlled study evaluated the early effects of canagliflozin on blood pressure (BP) in patients with type 2 diabetes mellitus (T2DM) and hypertension. Patients were randomized to canagliflozin 300 mg, canagliflozin 100 mg, or placebo for 6 weeks and underwent 24-hour ambulatory BP monitoring before randomization, on day 1 of treatment, and after 6 weeks. The primary endpoint was change in mean 24-hour systolic BP (SBP) from baseline to week 6. Overall, 169 patients were included (mean age, 58.6 years; glycated hemoglobin, 8.1%; seated BP 138.5/82.7 mm Hg). At week 6, canagliflozin 300 mg provided greater reductions in mean 24-hour SBP than placebo (least squares mean -6.2 vs -1.2 mm Hg, respectively; P=.006). Numerical reductions in SBP were observed with canagliflozin 100 mg. Canagliflozin was generally well tolerated, with side effects similar to those reported in previous studies. These results suggest that canagliflozin rapidly reduces BP in patients with T2DM and hypertension.

Frequent monitoring of A1C during pregnancy as a treatment tool to guide therapy.

OBJECTIVE: No guidelines for A1C measurement exist for women with gestational diabetes mellitus (GDM). The aim of this study was to document the rate of A1C decline in women with GDM. RESEARCH DESIGN AND METHODS: Women with GDM in the Santa Barbara County Endocrine Clinic are managed with a carbohydrate-restricted diet and self-monitored blood glucose before and 1-h postprandial. Insulin is started if the preprandial glucose concentration is ≥90 mg/dl and/or a 1-h postprandial glucose concentration is ≥120 mg/dl. Capillary A1C was tested weekly using the DCA2000+ analyzer. RESULTS: Twenty-four women with GDM (aged 29.0 ± 7.3 years) with initial A1C ≥7.0% were recruited. Baseline A1C was 8.8 ± 1.8%. Mean A1C decline was 0.47% per week (range 0.10-1.15%); the maximum was 4.3% in 4 weeks. CONCLUSIONS: This study documents rapid decline in A1C during pregnancy and the utility of weekly A1C to guide therapy.

Waiting for HAPO.

The recent global increase in gestational diabetes has paralleled the increased prevalence of obesity and type 2 diabetes. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study is an attempt to establish gestational diabetes diagnostic criteria as well as to clarify the accurate glucose threshold for the relationship between maternal hyperglycaemia and adverse perinatal outcomes. Although five international workshops have convened to address the importance of gestational diabetes, a resolution towards a general consensus for diagnosis and clinical management of gestational diabetes has not been achieved. Such a resolution may never appear, much like the outcome in the play Waiting for Godot, a character who in the end never arrives, and may not even exist. The accompanying article by Mathiesen and Vaz highlights the fetal, neonatal and maternal risks that accompany inadequate glycaemic control during pregnancies complicated by diabetes, even in the presence of only mild maternal hyperglycaemia. Diet, exercise and an optimised treatment regimen based on regular pre- and postprandial monitoring of blood glucose are essential throughout pregnancy. Pivotal to this goal is the recognition that insulin requirements in pregnancy are distinct from those of the prepregnancy state, and that these requirements change throughout gestation, labour and lactation.