期刊
JOURNAL OF DIABETES INVESTIGATION
卷 13, 期 6, 页码 965-974出版社
WILEY
DOI: 10.1111/jdi.13749
关键词
Glucagon-like peptide-1 receptor agonists; Glucose toxicity; Insulin-glucagon-like peptide-1 receptor agonist relay regimen
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Novo Nordisk Pharma Ltd.
- Astellas
- Novo Nordisk
- Ono Pharmaceutical Co. Ltd.
- Takeda
- Mitsubishi Tanabe Pharma Corp.
- Sumitomo Dainippon Pharma
- Novartis
- Eli Lilly
- MSD
The study found that GLP-1 receptor agonists can effectively lower blood glucose levels in diabetic patients, even without prior glycemic control. However, for insulinopenic type 2 diabetes patients, prior glycemic control with insulin may help overcome glucose toxicity-induced GLP-1 resistance.
Aims/Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP-1 receptor in an animal study. To examine this hypothesis clinically, we compared the glucose-lowering effects of GLP-1 receptor agonist liraglutide with and without prior glycemic control. Materials and Methods In an open-label, parallel trial, participants with poorly controlled type 2 diabetes were recruited and randomized to receive once-daily insulin therapy, degludec (Insulin-GLP-1 RA relay group, mean 16.8 +/- 11.4 IU/day), for 12 weeks and then liraglutide for 12 weeks or subcutaneous injections of GLP-1 RA, liraglutide (GLP-1 RA first group, 0.9 mg), for 24 weeks. The primary efficacy end-points consisted of changes in the levels of fasting plasma glucose and glycated hemoglobin (HbA1c). Results The median fasting plasma glucose and HbA1c before the study were 210.0 mg/dL and 9.8%, respectively. The levels of fasting plasma glucose and HbA1c significantly decreased in the Insulin-GLP-1 RA relay group (P < 0.001) and GLP-1 RA first group (P < 0.001) by week 24, although no intergroup differences were observed. The reduction of HbA1c in the Insulin-GLP-1 RA relay group tended to be larger than that in the GLP-1 RA first group in the lowest CPR (C-peptide immunoreactivity) quartile (P = 0.072). The adverse events consisted of gastrointestinal problems, followed by hypoglycemia. Conclusions The GLP-1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type 2 diabetes. However, in participants with insulinopenic type 2 diabetes, prior glycemic control with insulin might overcome glucose toxicity-induced GLP-1 resistance.
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