Insulin‐associated weight gain in obese type 2 diabetes mellitus patients: What can be done?

Abstract

Insulin therapy (IT) is initiated for patients with type 2 diabetes mellitus when glycaemic targets are not met with diet and other hypoglycaemic agents. The initiation of IT improves glycaemic control and reduces the risk of microvascular complications. There is, however, an associated weight gain following IT, which may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to 9 kg insulin-associated weight gain (IAWG) is reported to occur in the first year of initiating IT, predominantly caused by adipose tissue. The potential causes for this weight gain include an increase in energy intake linked to a fear of hypoglycaemia, a reduction in glycosuria, catch-up weight, and central effects on weight and appetite regulation. Patients with type 2 diabetes who are receiving IT often have multiple co-morbidities, including obesity, that are exacerbated by weight gain, making the management of their diabetes and obesity challenging. There are several treatment strategies for patients with type 2 diabetes, who require IT, that attenuate weight gain, help improve glycaemic control, and help promote body weight homeostasis. This review addresses the effects of insulin initiation and intensification on IAWG, and explores its potential underlying mechanisms, the predictors for this weight gain, and the available treatment options for managing and limiting weight gain.

Very low‐energy and low‐energy formula diets: Effects on weight loss, obesity co‐morbidities and type 2 diabetes remission – an update on the evidence for their use in clinical practice

“…Intensive multicomponent lifestyle interventions consisting of energy restriction, physical activity and behaviour change, alongside patient education, remain the cornerstone in the management of patients with both obesity and T2D (Brown et al . ) and have been used to promote weight loss in people with T2D (Franz et al . ; Terranova et al .…”

“…Weight loss remains the primary nutritional management strategy for adults with overweight or obesity and T2D (Dyson et al 2018), with weight losses of greater than 5% bodyweight leading to improvements in glycaemia, blood lipids, insulin sensitivity and blood pressure (Albu et al 2010;Franz et al 2015). Intensive multicomponent lifestyle interventions consisting of energy restriction, physical activity and behaviour change, alongside patient education, remain the cornerstone in the management of patients with both obesity and T2D (Brown et al 2017a) and have been used to promote weight loss in people with T2D (Franz et al 2015;Terranova et al 2015). When compared with standardised diabetes care in those with T2D, using an intensive multicomponent lifestyle intervention that included meal replacements, a lowfat diet and physical activity has been found to produce greater weight loss, improvements in glycaemia and T2D remission (Gregg et al 2012;Esposito et al 2014).…”

“…In a systematic review of the effects of specialist Tier 3 weight management interventions for adults in the UK, weight reduction in the majority of studies ranged between 2 and 6 kg (Brown et al . ,b). While a 5–10% bodyweight loss can have significant health benefits, weight loss of this magnitude has been suggested to be insufficient to give sustained and noticeable benefits in those with greater body mass indexes (BMI, ≥35 kg/m 2 ), which are often associated with serious medical conditions (SIGN ).…”

Efficacy and Safety of Insulin Glargine 300 U/mL in North Americans and Non-North Americans with Type 2 Diabetes: A Patient-Level Meta- Analysis of the EDITION 1, 2 and 3 Studies

“…Nevertheless, regional differences did not have an influence on weight when Gla-300 was used, since weight increased by less than 1 kg in both North American and non-North American participants on Gla-300. The risk of weight gain is one of the major concerns that delay timely introduction or intensification of insulin therapy [28][29][30]. Consequently, the observed neutral effect of Gla-300 on weight is promising and warrants further investigation.…”

“…One of the possible causes may be the more even PK and PD profile and longer duration of action of Gla-300, extending glucose control well beyond 24 hours [22]. It has been suggested that the PK profiles of traditional intermediate-acting human insulin which show a pronounced peak effect [31] may potentiate nocturnal hypoglycemia, compensatory eating behavior, and glucose variability that lead to weight gain [29]. Gla-300 provides predictable and stable 24-hour glycemic control as a result of low fluctuation (low within-day variability) and high reproducibility (low between-day variability) in insulin exposure [32] which may preclude adverse effects like hypoglycemia and associated weight gain.…”