The role of Recent Pharmacotherapeutic Options on the Management of Treatment Resistant Type 2 Diabetes

ABSTRACT

Introduction

Type 2 diabetes mellitus is a complex progressive disease leading to chronic hyperglycemia due to insulin resistance and pancreatic beta-cell failure. Intensification of treatment regimens is often necessary due to the overall decline in insulin secretion. Unfortunately, many patients are unable to achieve optimal glycemic control despite the standard of care and thus may be classified as ‘treatment resistant’.

Areas Covered

Newer pharmacotherapeutic agents, either injectable or oral, such as Glucagon-like-peptide-1 receptor agonists (GLP-1RA) and Sodium-glucose Cotransporter-2 (SGLT2) inhibitors are, herein, described. These agents can be used as single agents or fixed combinations that reduce glycemia while lessening the risk for hypoglycemia and renal and cardiovascular diseases.

Expert opinion

If individualized target HbA1c is not obtained despite diet, lifestyle, and metformin therapy, then additional oral and injectable therapies should be considered. This may include newer agents such as GLP-1RA and SGLT2 inhibitors alone or in combination that provide renal protection and reduce cardiovascular and hypoglycemic risks. These newer agents have substantial potential for lowering HbA1c through differing but complementary mechanisms. Use of new insulin analogs with GLP-1RA preparations either alone or in fixed-ratio combinations, such as glargine/lixisenatide and degludec/liraglutide, can also reduce the multiple drug adherence burden while improving glycemic control.

KEYWORDS:

• Treatment resistant
• type 2 diabetes mellitus
• glucagon-like peptide-1 receptor agonists
• sodium-glucose co-transporter-2 inhibitors
• fixed-ratio combinations

Article highlights

• Poor glycemic control in patients with type 2 diabetes mellitus on multiple oral medications, which may occur in more than 7% of patients, may be due to a variety of factors, including challenges with adherence, extreme obesity, mental health status, and comorbid conditions and medications.

• GLP-1RAs and SGLT2i are newer agents that can improve glycemic control for patients on multiple oral agents and may be particularly efficacious when used in combination.

• Fixed-dose ratio combinations reduce the injection burden and may provide weight loss benefit in patients already using insulin.

• Addressing barriers to optimal glycemic control such as obesity and adherence is an important first step in managing treatment-resistant diabetes mellitus. That being said, if individualized target HbA1c is not obtained despite diet, lifestyle, and metformin therapy, then additional oral and injectable therapies must be considered.

• Moving forward, future progress in the pharmacotherapeutic options for type 2 diabetes mellitus will continue to rely on novel mechanisms of action for glucose-lowering and end organ targeted protection. Studies examining the effects of combination therapy and simplifying therapeutic regimens continue to be warranted.

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no 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

One reviewer has received support from Kowa Company Ltd. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.