LAUSR

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.