Pharmacodynamics, pharmacokinetics, safety and tolerability of the novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist RG7697 after single subcutaneous administration in healthy subjects

2017 ◽  
Vol 19 (10) ◽  
pp. 1446-1453 ◽  
Author(s):  
Agnès Portron ◽  
Shirin Jadidi ◽  
Neena Sarkar ◽  
Richard DiMarchi ◽  
Christophe Schmitt
Keyword(s):  
Healthy Subjects ◽  
Subcutaneous Administration ◽  
The Novel ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1998 ◽  
Vol 95 (6) ◽  
pp. 719-724 ◽  
Author(s):  
C. Mark B. EDWARDS ◽  
Jeannie F. TODD ◽  
Mohammad A. GHATEI ◽  
Stephen R. BLOOM
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Healthy Subjects ◽  
Therapeutic Potential ◽  
Double Blind ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

Effects of sucralose on insulin and glucagon-like peptide-1 secretion in healthy subjects: a randomized, double-blind, placebo-controlled trial

Nutrition ◽  
2018 ◽  
Vol 55-56 ◽  
pp. 125-130 ◽  
Author(s):  
Amornpan Lertrit ◽  
Sasinee Srimachai ◽  
Sunee Saetung ◽  
Suwannee Chanprasertyothin ◽  
La-or Chailurkit ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Controlled Trial ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Postprandial glucose, insulin and glucagon-like peptide 1 responses to sucrose ingested with berries in healthy subjects

2011 ◽  
Vol 107 (10) ◽  
pp. 1445-1451 ◽  
Author(s):  
Riitta Törrönen ◽  
Essi Sarkkinen ◽  
Tarja Niskanen ◽  
Niina Tapola ◽  
Kyllikki Kilpi ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Serum Insulin ◽  
Venous Blood ◽  
Postprandial Glucose ◽  
Carbohydrate Ingestion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Meal Ingestion ◽  
Single Blind ◽  
Modest Effect

Berries are often consumed with sucrose. They are also rich sources of polyphenols which may modulate glycaemia after carbohydrate ingestion. The present study investigated the postprandial glucose, insulin and glucagon-like peptide 1 (GLP-1) responses to sucrose ingested with berries, in comparison with a similar sucrose load without berries. A total of twelve healthy subjects were recruited to a randomised, single-blind, placebo-controlled crossover study. They participated in two meal tests on separate days. The berry meal was a purée (150 g) made of bilberries, blackcurrants, cranberries and strawberries with 35 g sucrose. The control meal included the same amount of sucrose and available carbohydrates in water. Fingertip capillary and venous blood samples were taken at baseline and at 15, 30, 45, 60, 90 and 120 min after starting to eat the meal. Glucose, insulin and GLP-1 concentrations were determined from the venous samples, and glucose also from the capillary samples. Compared to the control meal, ingestion of the berry meal resulted in lower capillary and venous plasma glucose and serum insulin concentrations at 15 min (P = 0·021,P < 0·007 andP = 0·028, respectively), in higher concentrations at 90 min (P = 0·028,P = 0·021 andP = 0·042, respectively), and in a modest effect on the GLP-1 response (P = 0·05). It also reduced the maximum increases of capillary and venous glucose and insulin concentrations (P = 0·009,P = 0·011 andP = 0·005, respectively), and improved the glycaemic profile (P < 0·001 andP = 0·003 for capillary and venous samples, respectively). These results suggest that the glycaemic control after ingestion of sucrose can be improved by simultaneous consumption of berries.

scholarly journals Pharmacokinetic Study of SKL-18287, a Novel Long-Acting Glucagon-Like Peptide-1 Receptor Agonist, in Rats, Monkeys and Mini-Pigs

Drug Research ◽  
2019 ◽  
Vol 69 (09) ◽  
pp. 479-486
Author(s):  
Mitsuaki Takeuchi ◽  
Masayuki Okamoto ◽  
Miyuki Tamura ◽  
Takayo Murase ◽  
Nobuhide Watanabe
Keyword(s):  
Half Life ◽  
Animal Species ◽  
Subcutaneous Administration ◽  
The United States ◽  
Pharmacokinetic Parameters ◽  
Target Tissue ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Mini Pigs

Abstract Background Long-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for treatment of type 2 diabetes (T2DM) in the United States, the European Union, and Japan. In our previous work, we designed and characterized a novel GLP-1 RA, SKL-18287. This RA consists of only natural L-amino acids, and is believed to exist in an oligomer form in systemic circulation. This unique feature may allow high biological stability and a long-lasting glucose lowering effect in T2DM treatment. In the present study, we investigated the pharmacokinetic properties of SKL-18287 in rats, monkeys, and mini-pigs. Tissue distributions of radioactivity were also studied in rats after subcutaneous administration of [3H]-SKL-18287. Methods Plasma concentrations of SKL-18287 were measured by LC-MS/MS after intravenous and subcutaneous administration of SKL-18287 in rats, monkeys, and mini-pigs. Pharmacokinetic parameters were then calculated and compared among these animal species. Tissue concentrations of radioactivity were determined by liquid scintillation counting following sample combustion, after subcutaneous administration of [3H]-SKL-18287 to rats. Results SKL-18287 showed an extended half-life of over 5 h, with good subcutaneous bioavailability, in all animal species. Prediction of the pharmacokinetic profiles of SKL-18287 in humans using an animal scale-up approach revealed an SKL-18287 half-life of 14.8 h. The radioactivity concentration in the pancreas, a target tissue of GLP-1RA, was relatively higher than in other tissues, until 12 h after [3H]-SKL-18287 administration. Conclusion SKL-18287 might be sufficient to maintain an effective concentration for a once-daily treatment for T2DM, and is a unique GLP-1 RA with a pancreas-selective feature.

scholarly journals Perspectives of Antidiabetic Drugs in Diabetes With Coronavirus Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Bao Sun ◽  
Shiqiong Huang ◽  
Jiecan Zhou
Keyword(s):  
Viral Infections ◽  
Sglt2 Inhibitors ◽  
The Novel ◽  
Antidiabetic Agents ◽  
Dipeptidyl Peptidase 4 ◽  
Sodium Glucose Cotransporter ◽  
Coronavirus Infection ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Diabetes mellitus (DM) increases the risk of viral infections especially during the period of poor glycemic controls. Emerging evidence has reported that DM is one of the most common comorbidities in the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, also referred to as COVID-19. Moreover, the management and therapy are complex for individuals with diabetes who are acutely unwell with suspected or confirmed COVID-19. Here, we review the role of antidiabetic agents, mainly including insulin, metformin, pioglitazone, dipeptidyl peptidase-4 (DPP4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists in DM patients with coronavirus infection, addressing the clinical therapeutic choices for these subjects.

Jabuticaba juice improves postprandial glucagon-like peptide-1 and antioxidant status in healthy adults: a randomized crossover trial

2021 ◽  
pp. 1-29
Author(s):  
Marina V. Geraldi ◽  
Cínthia B. B. Cazarin ◽  
Marcelo Cristianini ◽  
Ana C. Vasques ◽  
Bruno Geloneze ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Healthy Subjects ◽  
Antioxidant Status ◽  
Metabolic Diseases ◽  
Area Under The Curve ◽  
C Peptide ◽  
Test Product ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Carbohydrate Meal

Abstract Jabuticaba is a Brazilian berry rich in polyphenols, which may exert beneficial effects on metabolic diseases. This randomized crossover study aimed to determine the effects of jabuticaba juice (250 ml in a portion) on postprandial response. Sixteen healthy subjects (11 women; 5 men; 28.4 ± 3.8 years old; body mass index (BMI) 21.7 ± 2.3 kg m−2) consumed two test products after fasting overnight in a randomized controlled crossover design. Each test product portion had a similar composition of sugar components: 250 mL water with glucose, fructose, colored with artificial non-caloric food colorings (placebo); and 250 mL of jabuticaba juice. Beverages were administered immediately before a carbohydrate meal. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min after each test product to analyze the concentrations of glucose, insulin, C-peptide, antioxidant capacity, plasma glucagon-like peptide-1 (GLP-1), and appetite sensations. Compared to the placebo, the intake of jabuticaba juice resulted in a higher GLP-1 response as the area under the curve (AUC) and peaking at 60 min. Jabuticaba juice also resulted in higher antioxidant capacity. Postprandial glucose, insulin, C-peptide levels, and appetite sensations were not significantly different between tests. In conclusion, 250 mL of jabuticaba juice before a carbohydrate meal was able to improve the antioxidant status and GLP-1 concentrations in healthy subjects.

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