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- Alsalim, Wathik, et al.
(författare)
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Different glucagon effects during DPP-4 inhibition versus SGLT-2 inhibition in metformin-treated type 2 diabetes patients
- 2018
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 20:7, s. 1652-1658
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Previous studies have shown that dipeptidyl peptidase (DPP)-4 inhibition lowers glucagon levels whereas sodium-glucose co-transporter 2 (SGLT-2) inhibition increases them. This study evaluated the extent of these opposite effects in a direct comparative head-to-head study. Methods: In a single-centre, randomized study with a cross-over design, 28 metformin-treated patients with type 2 diabetes (T2D) (mean age, 63 years; baseline HbA1c, 6.8%) were treated with vildagliptin (50 mg twice daily) or dapagliflozin (10 mg once daily) for 2 weeks, with a 4-week wash-out period between the two separate treatments. After each treatment period, a meal test was undertaken, with measurements of islet and incretin hormones and 4-hour area under the curve (AUC) levels were estimated. Results: Fasting glucagon (35.6 ± 2.5 vs 39.4 ± 3.4 pmoL/L; P = .032) and postprandial glucagon (4-hour AUCglucagon, 32.1 ± 2.3 vs 37.5 ± 2.7 nmoL/L min; P = .001) were ~15% lower after vildagliptin compared to dapagliflozin treatment. This was associated with stronger early (15 minute) C-peptide response and higher 4-hour AUCC-peptide (P < .010), higher 4-hour AUC of the intact form of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) (P < .001) and lower 4-hour AUC of total GIP and GLP-1 (P < .001). Conclusion: Treatment with DPP-4 inhibition with vildagliptin results in 15% lower fasting and postprandial glucagon levels compared to SGLT-2 inhibition with dapagliflozin. DPP-4 inhibition also induces more rapid insulin secretion and higher levels of intact incretin hormones, resulting in stronger feedback inhibition of incretin hormone secretion than SGLT-2 inhibition.
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| 2. |
- Farngren, Johan, et al.
(författare)
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Effects on the glucagon response to hypoglycaemia during DPP-4 inhibition in elderly subjects with type 2 diabetes : A randomized, placebo-controlled study
- 2018
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 20:8, s. 1911-1920
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Maintainance of glucagon response to hypoglycaemia is important as a safeguard against hypoglycaemia during glucose-lowering therapy in type 2 diabetes. During recent years, DPP-4 (dipeptidyl peptidase-4) inhibition has become more commonly used in elderly patients. However, whether DPP-4 inhibition affects the glucagon response to hypoglycaemia in the elderly is not known and was the aim of this study. Methods: In a single-centre, double-blind, randomized, placebo-controlled crossover study, 28 subjects with metformin-treated type 2 diabetes (17 male, 11 female; mean age, 74years [range 65-86]; mean HbA1c, 51.5mmol/mol [6.9%]) received sitagliptin (100mg once daily) as add-on therapy or placebo for 4weeks with a 4-week washout period in between. After each treatment period, the subjects underwent a standard breakfast test, followed by a 2-step hyperinsulinaemic hypoglycaemic clamp (target 3.5 and 3.0mmol/L), followed by lunch. Results: Glucagon levels after breakfast and lunch, and the glucagon response at 3.5mmol/L, were lower after sitagliptin than after placebo. However, the glucagon response to hypoglycaemia at 3.1mmol/L did not differ significantly between the two. Similarly, the noradrenaline, adrenaline and cortisol responses were lower with sitagliptin than with placebo at 3.5mmol/L, but not at 3.1mmol/L glucose. Responses in pancreatic polypeptide did not differ between the two. Conclusions: Elderly subjects with metformin-treated type 2 diabetes have lower glucagon levels at 3.5mmol/L glucose, but maintain the glucagon response to hypoglycaemia at 3.1mmol/L during DPP-4 inhibition, which safeguards against hypoglycaemia and may contribute to decreasing the risk of hypoglycaemia by DPP-4 inhibition in this age group.
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| 4. |
- Natali, Andrea, et al.
(författare)
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Metformin is the key factor in elevated plasma growth differentiation factor-15 levels in type 2 diabetes : A nested, case–control study
- 2019
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 21:2, s. 412-416
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Tidskriftsartikel (refereegranskat)abstract
- Produced as a tissue defence response to hypoxia and inflammation, growth differentiation factor-15 (GDF-15) is elevated in people receiving metformin treatment. To gain insight into the relationship of GDF-15 with metformin and major cardiovascular risk factors, we analysed the data from the SUMMIT cohort (n = 1438), a four-centre, nested, case–control study aimed at verifying whether biomarkers of atherosclerosis differ according to the presence of type 2 diabetes and cardiovascular disease. While in univariate analysis, major cardiovascular risk factors, with the exception of gender and cholesterol, increased similarly and linearly across GDF-15 quartiles, the independent variables associated with GDF-15, both in participants with and without diabetes, were age, plasma creatinine, N-terminal pro-brain natriuretic peptide, diuretic use, smoking exposure and glycated haemoglobin. In participants with diabetes, metformin treatment was associated with a 40% rise in GDF-15 level, which was independent of the other major factors, and largely explained their elevated GDF-15 levels. The relatively high GDF-15 bioavailability might partly explain the protective cardiovascular effects of metformin.
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