SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans

SCO-267 is a full agonist of the free fatty acid receptor 1 (GPR40), which regulates the secretion of islet and gut hormones. In this phase 1 study, we aimed to evaluate the clinical profile of single and multiple once-daily oral administration of SCO-267 in healthy adults and patients with diabetes. Plasma SCO-267 concentration was seen to increase in a dose-dependent manner after administration, and its plasma exposure was maintained for 24 h. Repeated dose did not alter the pharmacokinetic profile of SCO-267 in healthy adults. SCO-267 was generally safe and well tolerated at all evaluated single and multiple doses. Single and repeated doses of SCO-267 stimulated the secretion of insulin, glucagon, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and peptide YY in healthy adults. Furthermore, a single dose of SCO-267 stimulated the secretion of these hormones, decreased fasting hyperglycemia, and improved glycemic control during an oral glucose tolerance test in patients with diabetes, without inducing hypoglycemia. This study is the first to demonstrate the clinical effects of a GPR40 full agonist. SCO-267 is safe and well tolerated and exhibits once-daily oral dosing potential. Its robust therapeutic effects on hormonal secretion and glycemic control make SCO-267 an attractive drug candidate for the treatment of diabetes.

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SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans

Diabetes ◽

10.2337/db21-0451 ◽

2021 ◽

pp. db210451

Author(s):

Harunobu Nishizaki ◽

Osamu Matsuoka ◽

Tomoya Kagawa ◽

Akihiro Kobayashi ◽

Masanori Watanabe ◽

...

Keyword(s):

Glycemic Control ◽

Hormone Secretion ◽

Full Agonist ◽

Gut Hormone

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Association of hemoglobin H (HbH) disease with hemoglobin A1c and glycated albumin in diabetic and non-diabetic patients

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2020-1563 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Dabao He ◽

Wenbin Kuang ◽

Xiaoling Yang ◽

Miao Xu

Keyword(s):

Diabetes Mellitus ◽

Glycemic Control ◽

High Performance ◽

Hemoglobin A1c ◽

Glycated Albumin ◽

Healthy Adults ◽

Oral Glucose ◽

Diabetic Patients ◽

Discriminative Ability ◽

Hbh Disease

Abstract Objectives Hemoglobin A1c (HbA1c) and glycated albumin (GA) are glycemic control status indicators in patients with diabetes mellitus. Hemoglobin H (HbH) disease is a moderately severe form of α-thalassemia. Here we examine the usefulness of HbA1c and GA in monitoring glycemic control in patients with HbH disease. Methods HbA1c, GA, and an oral glucose tolerance test were performed in 85 patients with HbH disease and 130 healthy adults. HbA1c was measured using five methods, including two systems based on cation-exchange high-performance liquid chromatography (Variant II Turbo 2.0 and Bio-Rad D100), a capillary zone electrophoresis method (Capillarys 3 TERA), a boronate affinity HPLC method (Premier Hb9210), and an immunoassay (Cobas c501). Results Significant lower levels of HbA1c were observed in patients with HbH disease than in healthy adults. In contrast, GA showed no statistically significant differences between participants with and without HbH disease. A considerable number of diabetic patients with HbH disease would be missed if using HbA1c as a diagnostic criterion for diabetes mellitus. Conclusions GA but not HbA1c is suitable for monitoring glycemic control in patients with HbH disease that can modify the discriminative ability of HbA1c for diagnosing diabetes.

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Personalized Postprandial Glucose Response–Targeting Diet Versus Mediterranean Diet for Glycemic Control in Prediabetes

10.2337/figshare.14807184 ◽

2021 ◽

Author(s):

Orly Ben-Yacov ◽

Anastasia Godneva ◽

Michal Rein ◽

Smadar Shilo ◽

Dmitry Kolobkov ◽

...

Keyword(s):

Glycemic Control ◽

Dietary Intervention ◽

Postprandial Glucose ◽

Dietary Advice ◽

Oral Glucose ◽

Clinical Effects ◽

Glucose Levels ◽

The Mean ◽

Daily Time

OBJECTIVE To compare the clinical effects of a Personalized Postprandial-Targeting (PPT) diet vs a Mediterranean (MED) diet, on glycemic control and metabolic health in prediabetes. RESEARCH DESIGN AND METHODS We randomly assigned adults with prediabetes (n=225) to follow a MED diet or a PPT diet for a 6-month dietary intervention and additional 6-month follow-up. The PPT diet relies on a machine-learning algorithm that integrates clinical and microbiome features to predict personal postprandial-glucose-responses (PPGR). During the intervention, all participants were connected to continuous glucose monitoring (CGM) and self-reported dietary intake using a smartphone application. RESULTS Among 225 participants randomized (58.7% women; mean±SD age, 50±7 years; BMI, 31.3±5.8 kg/m2; HbA1c, 5.9±0.2% (41±2.4 mmol/mol); fasting plasma glucose 114±12mg/dl [6.33±0.67 mmol/L]), 200 (89%) completed the 6-month intervention. A total of 177 participants additionally contributed 12-month follow-up data. Both interventions reduced the daily time with glucose levels above 140 mg/dl (7.8 mmol/L) and HbA1c levels, but reductions were significantly greater in PPT compared to MED. The mean 6-month change in ‘time above 140 mg/dl (7.8 mmol/L)’ was -0.3±0.8 hour/day and -1.3±1.5 hour/day for MED and PPT, respectively (95% CI between-group difference, -1.29 to -0.66; p<0.001). The mean 6-month change in HbA1c was -0.08±0.19% (-0.9±2.1 mmol/mol) and -0.16±0.24% (-1.7±2.6 mmol/mol) for MED and PPT, respectively (95% CI between-group difference, -0.14 to -0.02; p=0.007). The significant between-group differences maintained at 12-month follow-up. No significant differences were noted between the groups in an oral glucose tolerance test (OGTT, CGM-measured). CONCLUSIONS In this clinical trial in prediabetes, a PPT diet improved glycemic control significantly more than a MED diet as measured by daily time of glucose levels above 140 mg/dl (7.8 mmol/L) and HbA1c. These findings may have implications to dietary advice in clinical practice.

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Erratum. SCO-267, a GPR40 Full Agonist, Stimulates Islet and Gut Hormone Secretion and Improves Glycemic Control in Humans. Diabetes 2021;70:2364–2376

Diabetes ◽

10.2337/db22-er01b ◽

2021 ◽

pp. db22er01b

Author(s):

Harunobu Nishizaki ◽

Osamu Matsuoka ◽

Tomoya Kagawa ◽

Akihiro Kobayashi ◽

Masanori Watanabe ◽

...

Keyword(s):

Glycemic Control ◽

Hormone Secretion ◽

Full Agonist ◽

Gut Hormone

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Abstract #70: Supervised Autonomy with Diabetes Self-Management by Using Telemedicine Allows Better Glycemic Control in Patients with Diabetes

Endocrine Practice ◽

10.1016/s1530-891x(20)43917-5 ◽

2003 ◽

Vol 9 ◽

pp. 27

Author(s):

M. Rigla ◽

E. Brugués ◽

E. Gómez ◽

E. Hernando ◽

A. García ◽

...

Keyword(s):

Glycemic Control ◽

Self Management ◽

Patients With Diabetes ◽

Supervised Autonomy

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The evaluation of knowledge level and motivational components in patients with diabetes and their relationship to glycemic control

10.15303/rjeap.2016.si1.a31 ◽

2016 ◽

Author(s):

KÁLCZA JÁNOSI KINGA ◽

◽

PORDEA ANETT ◽

Keyword(s):

Glycemic Control ◽

Knowledge Level ◽

Patients With Diabetes

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Managing Cardiovascular Risk in Patients with Type 2 Diabetes – Challenges and Opportunities

European Cardiology Review ◽

10.15420/ecr.2010.6.4.31 ◽

2010 ◽

Vol 6 (4) ◽

pp. 31

Author(s):

Lars Rydén ◽

Linda Mellbin ◽

Klas Malmberg ◽

◽

...

Keyword(s):

Glucose Tolerance ◽

Clinical Trial Data ◽

Oral Glucose ◽

Lifestyle Modifications ◽

Oral Glucose Tolerance Testing ◽

Coronary Death ◽

Increased Risk ◽

Challenges And Opportunities ◽

Patients With Diabetes ◽

Multifactorial Approach

The prevalence of diabetes and its associated complications, such as cardiovascular disease (CVD), has increased over recent years and is expected to continue to rise dramatically. People with diabetes have a poor prognosis, with a substantially increased risk of coronary heart disease, coronary death, non-fatal myocardial infarction, stroke, and other vascular deaths compared with non-diabetic subjects. Conversely, studies have also shown that many patients with CVD have undiagnosed dysglycaemia and that already impaired glucose tolerance and newly detected diabetes are associated with an impaired prognosis. Thus, screening for such conditions, preferably with oral glucose tolerance testing, should be performed in all patients with CVD. Guidelines advocate a multifactorial approach to the management of prediabetes, diabetes and CVD. This includes lifestyle modifications as well as targets for glycaemic control, blood pressure, lipids, and other cardiometabolic risk factors. Although clinical trial data have demonstrated that target-driven strategies can improve outcomes in patients with diabetes, the implementation and execution of these regimens in clinical practice needs to improve.

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