Improving the treatment of patients with diabetes using insulin analogues: current findings and future directions

ABSTRACT

Introduction: The aim of insulin replacement in insulin-deficient people (type 1 diabetes, pancreatic causes of diabetes, long-standing type 2 diabetes) is to approximate the physiologic insulin action profile as closely as possible. However, short-acting human insulins start too slow and act too long, causing postprandial hyperglycemia and delayed hypoglycemia, while the insulin action profile of long-acting human insulins is too variable in duration and strength of action, leading to insufficient basal insulin covering and peak insulin levels after injection causing early nocturnal hypoglycemia. Insulin analogues were designed to overcome these shortcomings. In insulin-resistant people (type 2 diabetes), insulin analogues contribute to more efficient and safer insulin supplementation.

Areas covered: In this review, we describe the unmet needs for insulin therapy, the currently available short- and long-acting insulin analogues and some considerations on cardiovascular outcomes, use in special populations, and cost-effectiveness. Finally, we discuss what is new in the field of insulin analogues.

Expert opinion: The development of insulin analogues is an important step in diabetes treatment. Despite many patients meeting their glycemic targets with the newest analogues, hypoglycemic episodes remain a major problem. More physiologic insulin regimens, with glucose-sensitive or organ-targeting insulin analogues may be the answer to these issues.

KEYWORDS:

• Cardiovascular outcome
• diabetes
• human insulins
• insulin analogues

Article highlights

• The short-acting insulin analogues insulin lispro, aspart, and glulisine have a faster onset of action and a shorter duration of action than human insulins, leading to reduced risk in hypoglycemia, better postprandial glycaemic control, and slightly improved HbA1c.

• Faster-acting insulin aspart and ultra-rapid-acting insulin lispro are new formulations of respectively insulin aspart and insulin lispro with an even faster onset of action, allowing injection more closely before mealtime, which is more convenient in daily life and therefore improves quality of life.

• The long-acting insulin analogues were designed to have a more stable and flatter insulin action profile with a longer duration than the long-acting human insulins, leading to reduced hypoglycaemic episodes, full 24-h coverage of basal insulin needs and better glycaemic control.

• The first-generation long-acting insulin analogues insulin detemir and glargine U100 do not achieve a full 24-h coverage in all patients, necessitating twice-daily injections in some of them. Insulin glargine U100 still has a variable insulin action profile, causing hypoglycemia (especially nocturnal) in some patients.

• The newer long-acting insulin analogues insulin glargine U300 and degludec are more stable and act longer than insulin detemir and glargine U100, leading to less hypoglycemia (especially nocturnal), better 24-h coverage (making once-daily injection sufficient) and more flexible injection times, all of which improve quality of life.

• Insulin analogues can be used in children but the authorization of the different preparations is age-dependent based on regulatory and approval data.

• Insulin analogues can be used in pregnant women, with the most evidence for insulin aspart, lispro, and detemir. Insulin glulisine and degludec cannot be recommended in pregnancy due to lack of safety data.

• All rapid-acting insulin analogues are compatible with CSII, but insulin glulisine is associated with higher catheter occlusion rates and more symptomatic hypoglycemia.

This box summarizes key points contained in the article.

Declaration of interest

C Mathieu serves or has served on the advisory panel for Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Hanmi Pharmaceuticals, Roche, Medtronic, ActoBio Therapeutics, Pfizer and UCB. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for C Mathieu from Medtronic, Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Roche, Abbott, ActoBio Therapeutics and Novartis; C Mathieu serves or has served on the speakers bureau for Novo Nordisk, Sanofi, Merck Sharp and Dohme, Eli Lilly and Company, Boehringer Ingelheim, Astra Zeneca and Novartis. Financial compensation for these activities has been received by KU Leuven. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.