Re-examining insulin compared to non-insulin therapies for type 2 diabetes: when in the disease trajectory is insulin preferable?

ABSTRACT

In patients with type 2 diabetes secondary to excess nutrients and energy balance, relative – not absolute – insulin deficiency plays a key role in disease development and progression. Although patients with type 2 diabetes who have features of insulin resistance would usually have hyperinsulinemia, insulin therapy remains recommended by guidelines particularly when patients fail to achieve glycemic goals. This approach does not prevent complications particularly macrovascular complications. This raises a controversial question regarding the benefit of using exogenous insulin for glycemic control in patients with type 2 diabetes who have features of insulin resistance. To address this concern, the authors performed a literature search looking for either randomized trials or meta-analyses directly comparing exogenous insulin to non-insulin therapy in the treatment of patients with type 2 diabetes. Our main outcomes of interest were effect on glycemic control and insulin resistance at various time points in the usual trajectory of type 2 diabetes. In trials investigating early short-term initiation of intensive insulin therapy, insulin therapy was beneficial in rapidly achieving glycemic control and reversing glucotoxicity. Following the initial 2 weeks to 3 months of adequate glycemic control in patients on intensive insulin therapy, there is little evidence that continuing insulin therapy provides greater glycemic control or improves insulin resistance beyond what can be achieved with other therapies. In conclusion, long-term insulin use appears neutral if not potentially harmful with respect to insulin resistance and cardiovascular outcomes. While this review has limitations and should be dealt cautiously, it raises questions regarding the benefit of insulin in patients with type 2 diabetes with features of insulin resistance. Further research is needed to confirm these findings.

KEYWORDS:

• Insulin
• non-insulin therapy
• type 2 diabetes
• insulin resistance
• diabetic complications

Acknowledgments

An earlier version of the manuscript was presented as an oral presentation at the American Diabetes Association (Pride and Proud Meeting) in San Diego, California, USA in June 2017.

Declaration of interest

R Tanenberg obtains research funding from Novo-Nordisk. 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. Peer reviewers on this manuscript have no relevant financial relationships to disclose.

Author contributions

WJP was responsible for the concept of the paper. BMM was responsible for the design and initial manuscript. DMC, RJT, and WJP critically reviewed the manuscript

Additional information

Funding

This manuscript was not funded.