202206211211Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management

MINI REVIEW article Front. Endocrinol., 24 January 2017 | https://doi.org/10.3389/fendo.2017.00006

Type 2 diabetes mellitus is one of the leading causes of renal failure, ASCVD, non-traumatic lower limb amputation, blindness, and death worldwide. It is a serious chronic medical condition that requires a multidisciplinary team approach, consisting of healthcare professionals, dietitians, patient educators, patients, and their families. Lifestyle intervention designed to manage body weight and treat obesity, as well as patient education, are essential for all patients with diabetes. Treatment options may be individualized and medication(s) chosen based on a patient’s risk factors, current HbA1C level, medication efficacy, ease of use, patient’s financial situation/insurance/costs, and risk of side effects such as hypoglycemia and weight gain. Effectiveness of therapy must be evaluated as frequent as possible using diagnostic blood tests (HbA1C), as well as monitoring for development of diabetic complications (e.g., retinopathy, nephropathy, neuropathy). Furthermore, aggressive efforts from physicians and motivating patients for compliance are the two important aspects of the prevention and management of diabetes. Sociocultural issues should be carefully considered. For example, during religious fasting (e.g., during the holy month of Ramadan), the use of pharmacologic agents that induce hypoglycemia should be used with care and insulin doses (for example, premix formulations) should be appropriately titrated and the patient should be educated for blood glucose monitoring and breaking of fast as needed (43).

By the year 2030, >70% of people with T2DM shall reside in developing countries (44). Primary prevention of T2DM should be an urgent public health policy. The disease predominantly affects working-age people and therefore has a counterproductive economic impact, compounded by the frequent occurrence and interaction of T2DM with infectious diseases (such as AIDS and tuberculosis) (45). Evidence from landmark T2DM prevention trials indicates that lifestyle modification is more effective, cheaper, and safer than medication and provides sustained benefits. Lifestyle modification may be promising approach to T2DM prevention in developing countries. This will be useful for many ethnic groups in the U.S. as well, such as South Asian, Latino, Pima Indians, and African-American populations, which may face socioeconomic challenges similar to what is seen in developing countries. Cost-contained strategies to identify at-risk individuals, followed by the implementation of group-based, inexpensive lifestyle interventions (“comfortably uncomfortable” life, as lived by people in blue zones), seem to be the best options for resource-constrained settings. T2DM pathophysiology is increasingly understood as a mix of insulin resistance and secretory defects of β-cells (46).

Several options for pharmacologic therapy of lowering blood glucose are currently available, which have revolutionized long-term management of DM (47). Several antidiabetic drugs may have important CV complications, which the provider team should always be aware (48). The polypharmacy issues, management of diabetes, as well as hypertension, hyperlipidemia, and use of aspirin should be carefully explained to patients to ensure adherence to therapy to prevent significant CV morbidity and mortality. Careful attention should be paid to development of insulinopenic states by clinical assessment of C peptide and lack of control of HbA1C with multiple medications, and complete lack of secreted insulin conditions should be treated by initiation of appropriate insulin regimens. Every clinical encounter should also be utilized to explain the benefit of weight loss and motivated for such. Even though not yet conclusive, clinical trial and data support consideration of bariatric surgery as a possible strategy to monitor blood glucose levels and body weight, especially in morbid obesity (49). Balanced hypocaloric diets that cause weight loss must be adopted, and regular interactions with dietitian is a useful approach. Aerobic training and resistance training can control increasing lean mass in middle-aged and overweight/obese individuals. Behavioral strategies for weight loss should be encouraged in primary care settings and appropriate maintenance of body weight prior to conception may help after development of gestational diabetes. Weight loss may be particularly challenging for incapacitated patients and subjects with disabilities, so comprehensive approaches should be undertaken. Newer molecular studies have demonstrated the transcriptional link between inflammatory pathways and increased adipose tissue storage, contributing to insulin resistance (50). Drug repurposing of the anti-inflammatory agent for aphthous stomatitis, amlexanox, is currently undergoing trials as newer agents for management of diabetes (51).