Adjunct Therapy in Type 1 Diabetes: A Survey to Uncover Unmet Needs and Patient Preferences Beyond HbA1c Measures.

Background: Adjunct therapy can help patients with type 1 diabetes achieve glycemic goals while potentially mitigating some of the side effects of insulin. In this study, we used a patient survey to identify the unmet needs in type 1 diabetes therapy, patient views of treatment benefit-risk trade-offs, and patient preferences for the use of an adjunct therapy. Methods: A quantitative survey was sent to 2084 adults with type 1 diabetes in November 2017. "Jobs-to-be-done" and conjoint analyses were performed on survey responses to identify unmet needs and the importance of treatment-associated benefits and risks to patients. A 5-point Likert scale measured the importance and satisfaction with patients' current therapy, and with gaps relating to unmet needs. In the conjoint analysis, patients were asked to choose between "packages" of attributes of two doses of adjunct therapy (200 and 400 mg) and placebo, based on established benefits and side effects. Results: A total of 1313 patients (63%) responded. The greatest unmet needs identified were simplifying treatment, lowering/maintaining glycated hemoglobin (HbA1c), reducing mental effort, and increasing time in range (TIR). Conjoint analysis showed that reductions in body weight and TIR had the highest attribute importance (25% and 18%, respectively). The majority (93%) of patients had a preference for the adjunct therapy (either dose) over placebo. Conclusions: This survey highlights the importance of measures beyond HbA1c, such as treatment simplification and TIR, and patient preference for adjunct therapies that help address unmet needs in type 1 diabetes treatment

Gestational Diabetes Mellitus in Sardinia

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A Placebo-Controlled Trial of Pioglitazone in Subjects with Nonalcoholic Steatohepatitis

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Autoimmunity in gestational diabetes mellitus in Sardinia: a preliminary case-control report

<p>Abstract</p> <p>Background</p> <p>We previously reported a high prevalence (22.3%) of gestational diabetes mellitus (GDM) in a large group of Sardinian women, in contrast with the prevalence of Type 2 diabetes. Sardinia has an unusual distribution of haplotypes and genotypes, with the highest population frequency of HLA DR3 in the world, and after Finland, the highest prevalence of Type 1 diabetes and Autoimmune-related Diseases. In this study we preliminarily tested the prevalence of serological markers of Type 1 diabetes in a group of Sardinian GDM patients.</p> <p>Methods</p> <p>We determined glutamic decarboxylase antibodies (anti-GAD65), protein tyrosine phosphatase ICA 512 (IA2) antibodies (anti-IA2), and IAA in 62 GDM patients, and in 56 controls with matching age, gestational age and parity.</p> <p>Results</p> <p>We found a high prevalence and very unusual distribution of antibodies in GDM patients (38.8%), the anti-IA2 being the most frequent antibody. Out of all our GDM patients, 38.8% (24 of 62) were positive for at least one antibody. Anti-IA2 was present in 29.0 % (18 out of 62) vs. 7.1% (4 out of 56) in the controls (P < 0.001). IAA was present in 14.5% (9 out of 62) of our GDM patients, and absent in the control subjects (P < 0.001). Anti-GAD65 was also present in GDM patients, with a prevalence of 3.2% (2 out of 62) while it was absent in the control group (P = NS). Pre-gestational weight was significantly lower (57.78 ± 9.8 vs 65.9 ± 17.3 <it>P </it>= 0.04) in auto-antibodies- positive GDM patients.</p> <p>Conclusion</p> <p>These results are in contrast with the very low prevalence of all antibodies reported in Italy. If confirmed, they could indicate that a large proportion of GDM patients in Sardinia have an autoimmune origin, in accordance with the high prevalence of Type 1 diabetes.</p

The Extra-Glycemic Effect of Pioglitazone

Pioglitazone was demonstrated to have efficacy and durability of glycemic control in type 2 diabetes through several studies, and evidence has accumulated for its cardiovascular safety, as well as well as some positive, yet inconclusive results to prove its cardioprotective effect. Several other actions of pioglitazone beyond its glycemic effect are appreciable. The major side effects of pioglitazone are edema (with the potential of leading to chronic heart failure), weight gain, increased incidence of bone fractures and decreased hematocrit and hemoglobin. Its molecular action on the skeletal muscle, especially its anti-inflammatory effect, is a worthwhile, novel finding of out studies, considering its independence from the glucose-lowering effect. Thus, it is plausible that its anti-inflammatory effect precedes, and possibly leads to, insulin sensitization. In our study, we demonstrated that treatment with pioglitazone causes a normalization of inflammation at the molecular level in skeletal muscle of nondiabetic, insulin resistant women and showed, to the best of our knowledge, for the first time, that the improved insulin action which occurs after treatment with TZDs is associated to their anti-inflammatory action in polycystic ovarian syndrome. Moreover, despite the failure of troglitazone due its hepatotoxicity, we not only proved pioglitazone safe in terms of hepatic liver function tests, but -for the first time in a randomized, double-blind, placebo-controlled trial- demonstrated a positive effect of pioglitazone on metabolic and histological indexes of liver steatosis. Also, the positive effect of pioglitazone was shown also in patients with polycystic ovarian syndrome, who -despite having liver transaminases value within the normal range before being treated with TZD- consistently demonstrated a further lowering of transaminases levels after treatment with pioglitazone. Finally, the mechanism of TZD-induced mild anemia was carefully investigated, both among patients with type 2 diabetes and in a special population of insulin resistant, nondiabetic women characterized by hyperandrogenemia. The latter findings warrant further studies in male type 2 diabetic patients, in order to explore their hormonal status and dependence on pioglitazone. In summary, pioglitazone was shown to hold a pleiotropic mechanism of action, which grants not only the well-known anti-hyperglycemic effect, but also several other actions, independent from the glycemic efficacy, some of which make pioglitazone a valuable compound in the armamentarium of diabetologists, as well as gastroenterologists and gynecologists

Achieving postprandial glucose control with lixisenatide improves glycemic control in patients with type 2 diabetes on basal insulin: a post-hoc analysis of pooled data

Abstract Background To examine the impact on glycemic control of achieving postprandial glucose (PPG) target with lixisenatide, a once-daily glucagon-like peptide-1 receptor agonist approved in the US, in patients with uncontrolled type 2 diabetes (T2D) on basal insulin, an agent that primarily targets fasting plasma glucose. Methods A post hoc pooled analysis was conducted using clinical trial data extracted from the intent-to-treat subpopulation of patients with T2D who participated in the 24-week, phase 3, randomized, double-blind, placebo-controlled, 2-arm parallel-group, multicenter GetGoal-L (NCT00715624), GetGoal-Duo 1 (NCT00975286) and GetGoal-L Asia trials (NCT00866658). Results Data from 587 lixisenatide-treated patients and 484 placebo-treated patients were included. Patients on lixisenatide were more likely to achieve a PPG target of < 10 mmol/L (< 180 mg/dL) than placebo-treated patients (P < 0.001), regardless of baseline fasting plasma glucose (FPG) levels. More importantly, those who reached the PPG target experienced a significantly greater reduction in mean HbA1c, were more likely to achieve HbA1c target of < 53 mmol/mol (< 7.0%), and experienced weight loss. Those outcomes were achieved with no significant differences in the risk of symptomatic hypoglycemia compared with placebo. Conclusion Compared with placebo, addition of lixisenatide to basal insulin improved HbA1c and reduced PPG, without increasing hypoglycemia risk. These findings highlight the importance of PPG control in the management of T2D, and provide evidence that adding an agent to basal insulin therapy that also impacts PPG has therapeutic value for patients who are not meeting glycemic targets. Trial registration NCT00715624. Registered 15 July 2008, NCT00975286. Registered 11 September 2009, NCT00866658. Registered 20 March 2009

Pronounced Reduction Of Postprandial Glucagon By Lixisenatide: A Meta-Analysis Of Randomized Clinical Trials.

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels