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Effects on the glucagon response to hypoglycaemia during DPP-4 inhibition in elderly subjects with type 2 diabetes: A
Johan Farngren1, Margaretha Persson2, Bo Ahrén1
1Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
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, 74 years [range 65-86]; mean HbA1c, 51.5 mmol/mol [6.9%]) received sitagliptin (100 mg once daily) as add-on therapy or placebo for 4 weeks 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 3.0 mmol/L), followed by lunch.
Results:
Glucagon levels after breakfast and lunch, and the glucagon response at 3.5 mmol/L, were lower after sitagliptin than after placebo. However, the glucagon response to hypoglycaemia at 3.1 mmol/L did not differ significantly between the two. Similarly, the noradrenaline, adrenaline and cortisol responses were lower with sitagliptin than with placebo at 3.5 mmol/L, but not at 3.1 mmol/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 3.5 mmol/L glucose, but maintain the glucagon response to hypoglycaemia at 3.1 mmol/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.
Insights
Dipeptidyl peptidase-4 (DPP-4) inhibition in elderly type 2 diabetes patients on metformin does not impair the crucial glucagon response to hypoglycemia. This finding suggests DPP-4 inhibitors may help reduce hypoglycemia risk in this vulnerable population.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Geriatrics
Background:
- Glucagon response to hypoglycemia is vital for glucose homeostasis during diabetes treatment.
- Dipeptidyl peptidase-4 (DPP-4) inhibitors are increasingly used in elderly patients with type 2 diabetes.
- The effect of DPP-4 inhibition on the elderly's counter-regulatory hormonal response to hypoglycemia remains unclear.
Purpose of the Study:
- To investigate the impact of DPP-4 inhibition on the glucagon response to hypoglycemia in elderly patients with type 2 diabetes.
- To assess whether sitagliptin affects counter-regulatory hormone release during induced hypoglycemia.
Main Methods:
- A randomized, double-blind, placebo-controlled crossover study was conducted.
- 28 elderly patients with type 2 diabetes on metformin received sitagliptin or placebo for 4 weeks.
- Hypoglycemic clamps were used to induce low glucose levels (3.5 and 3.0 mmol/L) after a meal.
Main Results:
- Glucagon levels and response at 3.5 mmol/L were lower with sitagliptin compared to placebo.
- The glucagon response to hypoglycemia at 3.1 mmol/L was not significantly different between treatments.
- Adrenaline, noradrenaline, and cortisol responses were blunted at 3.5 mmol/L but not at 3.1 mmol/L with sitagliptin.
Conclusions:
- Elderly patients with type 2 diabetes on metformin maintain their glucagon response to hypoglycemia at 3.1 mmol/L during DPP-4 inhibition.
- DPP-4 inhibition may safeguard against hypoglycemia by preserving this critical counter-regulatory response.
- These findings suggest a potential role for DPP-4 inhibitors in reducing hypoglycemia risk in older adults with type 2 diabetes.
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