Exercise-Induced Hypoglycemia Risk

The risk of exercise-induced hypoglycemia seems to be similar for insulin degludec compared to insulin glargine in patients with T1DM, according to a study published online in Diabetes, Obesity and Metabolism.

The benefits of exercise apply to everyone, including those with T1DM. But people with T1DM can sometimes avoid exercising because of the fear of hypoglycemia.

Basal insulins vary in their pharmacodynamic profiles and duration of action. For example, insulin glargine has a half-life that is half as long as that of insulin degludec. Whether or not these differences affect exercise-induced hypoglycemia, though, has needed clarification.

The single-center randomized, open-label study included 40 individuals (35 men, 5 women), with a mean age of 33.9 years, BMI 23.9, peak VO₂ 39.4, HbA1c 7.7, and diabetes duration 16.7 years.¹

Researchers randomized participants to insulin degludec (Tresiba, 100 units/mL in 3-mL pre-filled investigational pens, PDS290; Novo Nordisk, Bagsvaerd, Denmark), followed by insulin glargine (Lantus, 100 units/mL in 3-mL SoloStar; Sanofi, Paris, France), or the opposite (insulin glargine followed by insulin degludec). As bolus insulin, participants received insulin aspart (NovoRapid, 100 units/mL in 3-mL FlexPen trademark; Novo Nordisk, Bagsvaerd, Denmark).

After an initial 14- to 28-day titration period to reach a 6-day steady-state period, participants performed 30 minutes of moderate-intensity cycling to reach 65% of peak VO₂. Before exercise, participants adjusted their lunchtime carbohydrate intake and reduced their aspart dose so that they would have consistent blood glucose levels before exercise. For 24 hours after exercise, researchers measured blood glucose, counter-regulatory hormones, and hypoglycemic episodes (blood glucose <56 mg/dL).

One participant dropped out, and the analysis included data on 39 individuals.

Key Results:

• Similar blood glucose decreases during exercise for insulin degludec vs insulin glargine

♦ Estimated treatment difference (ETD) for max blood glucose decrease: 0.14 mmol/L [95% CI -0.15, 0.42, P=0.34)

• Similar mean blood glucose during exercise

♦ ETD: -0.16 mmol/L, 95% CI -0.36, 0.05, P=0.13)

• No episodes of hypoglycemia occurred during exercise

• 24 hours after exercise: similar post-exercise mean blood glucose, counter-regulatory hormone response, number of hypoglycemic episodes, nocturnal hypoglycemia, need for carbohydrate, and total bolus dose of insulin

♦ Insulin degludec: 18 events in 13 patients

♦ Insulin glargine: 23 events in 15 patients

Because the study took place in a very tightly controlled environment, the findings may not generalize to real-life situations, the authors noted. For example, not adjusting carbohydrate intake and not reducing bolus dose before exercise could lead to hyperglycemia and different results.  In the study, participants also did not decrease the bolus dose after exercise, which can help prevent hypoglycemia. The authors noted, however, that the results were similar to a recent meta-analysis of seven clinical trials which looked at patient-reported exercise-related hypoglycemic episodes, and found no increased risk for insulin degludec compared to insulin glargine.²

“[T]his study demonstrated that the risk of hypoglycemia in T1D patients induced by moderate intensity exercise was low with insulin degludec and similar compared with insulin glargine,” concluded first author Time Heise of Profil in Neuss GmbH Germany, and colleagues at Swansea Univeristy (UK) and Novo Nordisk (Denmark, USA).

Take Home Points:

• Even though insulin glargine and insulin degludec have different pharmacodynamic profiles and duration of action, a small, highly controlled study has shown that study participants who used them have similar blood glucose concentrations during and after moderate intensity exercise.

• Participants experienced no hypoglycemia events during exercise.

• Counter-regulatory hormone response, hypoglycemic episodes, need for carbohydrate, and total bolus dose of insulin 24 hours after exercise were similar for insulin degludec and insulin glargine.

The study was sponsored by Novo Nordisk A/S. Four authors (Kirstine Stender-Petersen, Rasmus Rabol, Everton Rowe, and Hanne L. Haahr) are employees of Novo Nordisk.

References:

1. Heise T, et al. Similar risk of exercise-related hypoglycaemia for insulin degludec compared with insulin glargine in patients with type 1 diabetes: a randomised cross-over trial. Diabetes Obes Metab. 9 Oct 2015

2. Heller SR, et al. Exercise-related hypoglycemia occurs at similar frequency with insulin degludec and insulin glargine. Diabetes. 2013;62(Suppl. 1):A187.