Weight‐sparing effect of insulin detemir: a consequence of central nervous system‐mediated reduced energy intake?

Abstract

Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight‐sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter‐regulatory response to insulin through restoration of the hepatic–peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight‐sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.

What's in a Name? Classification of Diabetes Mellitus in Veterinary Medicine and Why It Matters

“…Pancreatic polypeptide deficiency has been identified in people with chronic pancreatitis and in rodent models, and could contribute to the development of DM . Identifying this deficiency in a diabetic patient could have implications for treatment such preference for a “hepato‐selective” insulin formulation (eg, insulin detemir) . In the few studies that have described the histopathologic abnormalities in the pancreatic islets of DM dogs, a decreased number of β‐cells paralleled a reduction in other cell types in the islets; a complete absence of islets was frequently reported but a detailed characterization of all cell types in the islets was not performed .…”

Using the cerebrospinal fluid to understand ingestive behavior

“…While both cause comparable reductions and maintenance of blood glucose, interestingly, diabetics who use the detemir formulation are able to effectively manage blood glucose without experiencing undesired weight gain relative to normal human insulin or insulin glargine [67,68]. We and others have also observed this in rodent models [69,70]. More recently we found that insulin detemir prevents weight gain due in part to an enhanced anorectic action in the CNS relative to other insulin formulations.…”

ISPAD Clinical Practice Consensus Guidelines 2018: Insulin treatment in children and adolescents with diabetes

“…In adults, studies with detemir have shown less weight gain, which has been observed also in children and adolescents . Although the precise mechanism remains unclear, it is likely that the weight‐sparing effect of insulin detemir can be explained by a combination of mechanisms …”

“…Glargine is often given once a day, but many children may need to be injected twice a day or combined with NPH to provide full daytime basal insulin coverage . Glargine can be given before breakfast, before dinner or at bedtime with equal effect, but nocturnal hypoglycemia occurs significantly less often after breakfast injection . When transferring to glargine as basal insulin, the total dose of basal insulin needs to be reduced by approximately 20% to avoid hypoglycemia .…”