Efficacy and Safety of Mini-Dose Glucagon for Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes

Haymond, Morey W.; DuBose, Stephanie N.; Rickels, Michael R.; Wolpert, Howard; Shah, Viral N.; Sherr, Jennifer; Weinstock, Ruth S.; Agarwal, Shivani; Verdejo, Alandra; Cummins, Martin J.; Newswanger, Brett; Beck, Roy W.

doi:10.1210/jc.2017-00591

Cited by 39 publications

(35 citation statements)

References 11 publications

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“…Nausea without vomiting has been reported infrequently after exposure to 150 mg of MDG (0 of 12 [15] and 3 of 17 [16] participants in previous studies), which is consistent with complaints in 2 of the 15 participants here. Although this is likely related to the established effect of glucagon to relax gastrointestinal smooth muscle (20), nausea occurred more often with a 300-mg dose of MDG (4 of 12 participants) (15) and is observed with or without vomiting in more than a third of individuals treated with 1-mg emergency doses of glucagon (21).…”

Section: Discussionsupporting

confidence: 90%

“…A nonaqueous liquid form of glucagon is currently in development with appropriate dose-dependent pharmacokinetic and pharmacodynamics responses when administered subcutaneously at doses of 75, 150, and 300 mg in adults with type 1 diabetes (15). A recent study demonstrated that 150 mg of this mini-dose glucagon (MDG) product was as effective as oral glucose tablets in correcting nonsevere hypoglycemia in adults with type 1 diabetes, enabling the avoidance of unnecessary caloric intake (16). In the current study, we sought to determine whether MDG given subcutaneously before aerobic exercise could prevent subsequent glucose lowering in adults with type 1 diabetes compared with no intervention and further to evaluate the glycemic responses seen with insulin reduction and glucose tablets approaches for mitigating exercise-associated hypoglycemia.…”

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confidence: 99%

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Mini-Dose Glucagon as a Novel Approach to Prevent Exercise-Induced Hypoglycemia in Type 1 Diabetes

et al. 2018

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Mini-Dose Glucagon as a Novel Approach to Prevent Exercise-Induced Hypoglycemia in Type 1 Diabetes

et al. 2018

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“… 11 Mini-doses of glucagon are effective in treating mild to moderate hypoglycemic episodes in both children 6 36 as well as adults. 16 …”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal, subcutaneous and intravenous glucagon delivery and subsequent glucose response in rats: a randomized controlled crossover trial

Dirnena-Fusini

Åm²,

Fougner

et al. 2018

BMJ Open Diab Res Care

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ObjectiveHypoglycemia is a frequent and potentially dangerous event among patients with diabetes mellitus type 1. Subcutaneous glucagon is an emergency treatment to counteract severe hypoglycemia. The effect of intraperitoneal glucagon delivery is sparsely studied. We performed a direct comparison of the blood glucose response following intraperitoneally, subcutaneously and intravenously administered glucagon.Research design and methodsThis is a prospective, randomized, controlled, open-label, crossover trial in 20 octreotide-treated rats. Three interventions, 1 week apart, in a randomized order, were done in each rat. All 20 rats were given intraperitoneal and subcutaneous glucagon injections, from which 5 rats were given intravenous glucagon injections and 15 rats received placebo (intraperitoneal isotonic saline) injection. The dose of glucagon was 5 µg/kg body weight for all routes of administration. Blood glucose levels were measured before and until 60 min after the glucagon/placebo injections.ResultsCompared with placebo-treated rats, a significant increase in blood glucose was observed 4 min after intraperitoneal glucagon administration (p=0.009), whereas after subcutaneous and intravenous glucagon administration significant increases were seen after 8 min (p=0.002 and p<0.001, respectively). In intraperitoneally treated compared with subcutaneously treated rats, the increase in blood glucose was higher after 4 min (p=0.019) and lower after 40 min (p=0.005) and 50 min (p=0.011). The maximum glucose response occurred earlier after intraperitoneal compared with subcutaneous glucagon injection (25 min vs 35 min; p=0.003).ConclusionsGlucagon administered intraperitoneally gives a faster glucose response compared with subcutaneously administered glucagon in rats. If repeatable in humans, the more rapid glucose response may be of importance in a dual-hormone artificial pancreas using the intraperitoneal route for administration of insulin and glucagon.

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“…The split total glucagon dose was delivered every 10 min during the 60 min exercise sessions. Mini-doses of glucagon were found to be efficacious and safe to treat mild hypoglycemia in adults with type 1 diabetes [ 85 ]. Successful hypoglycemia-treatment criteria were met for 94% when using a mini-dose of glucagon in comparison to 95% when giving oral glucose tablets.…”

Section: Future Directionsmentioning

confidence: 99%

Interstitial Glucose and Physical Exercise in Type 1 Diabetes: Integrative Physiology, Technology, and the Gap In-Between

2018

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Continuous and flash glucose monitoring systems measure interstitial fluid glucose concentrations within a body compartment that is dramatically altered by posture and is responsive to the physiological and metabolic changes that enable exercise performance in individuals with type 1 diabetes. Body fluid redistribution within the interstitial compartment, alterations in interstitial fluid volume, changes in rate and direction of fluid flow between the vasculature, interstitium and lymphatics, as well as alterations in the rate of glucose production and uptake by exercising tissues, make for caution when interpreting device read-outs in a rapidly changing internal environment during acute exercise. We present an understanding of the physiological and metabolic changes taking place with acute exercise and detail the blood and interstitial glucose responses with different forms of exercise, namely sustained endurance, high-intensity, and strength exercises in individuals with type 1 diabetes. Further, we detail novel technical information on currently available patient devices. As more health services and insurance companies advocate their use, understanding continuous and flash glucose monitoring for its strengths and limitations may offer more confidence for patients aiming to manage glycemia around exercise.

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Efficacy and Safety of Mini-Dose Glucagon for Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes

Abstract: Low-dose glucagon can successfully treat mild hypoglycemia and may be a useful alternative to treatment with oral carbohydrate when trying to avoid unnecessary caloric intake.

Cited by 39 publications

References 11 publications

Mini-Dose Glucagon as a Novel Approach to Prevent Exercise-Induced Hypoglycemia in Type 1 Diabetes

Mini-Dose Glucagon as a Novel Approach to Prevent Exercise-Induced Hypoglycemia in Type 1 Diabetes

Intraperitoneal, subcutaneous and intravenous glucagon delivery and subsequent glucose response in rats: a randomized controlled crossover trial

Interstitial Glucose and Physical Exercise in Type 1 Diabetes: Integrative Physiology, Technology, and the Gap In-Between

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