Summary

This article highlights that prediabetes increases the risk for ASCVD , the AACE emphasises that rather than a BMI-centric approach for management of patients with overweight/obesity, the clinicians should make use of the complications-centric model which incorporates 3 disease stages.

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) have recently released a consensus statement outlining the comprehensive management algorithm for Type 2 diabetes. The updated 2019 document has been published in the journal Endocrine Practice.

Management of Patients with Prediabetes

The primary goal of prediabetes management is weight loss. Current criteria for the diagnosis of prediabetes include impaired glucose tolerance, impaired fasting glucose, or insulin resistance (metabolic) syndrome. Any one of these factors is associated with a 5-fold increase in future T2D risk.

Key take-aways from the statement include:

1. Currently, No FDA approved medications (either weight-loss drugs or antihyperglycemic agents) exist exclusively for the management of prediabetes and/or prevention of T2D. However, antihyperglycemic medications such as metformin and acarbose scale down the risk of future diabetes in pts with prediabetes by 25-30%. Both medications are relatively well-tolerated and safe, and they may confer a CV risk benefit.
2. Glucagon-like peptide 1 (GLP1) receptor agonists are equally competent, as demonstrated by the profound effect of liraglutide 3 mg in safely preventing diabetes and restoring normoglycemia in the majority of subjects with prediabetes. However, owing to the lack of long-term safety data on GLP1 receptor agonists and the known adverse effects of TZDs, these agents should be considered only for patients failing more conventional therapies (i.e., lifestyle therapy and/or metformin).
3. As with diabetes, prediabetes increases the risk for ASCVD and such patients should be managed with lifestyle therapy and pharmacotherapy to achieve lipid and BP targets that will diminish the ASCVD risk.

Management of T2D in obese patients

Obesity is a chronic disease, and a long-term commitment to therapy is necessary. Weight loss should be considered in all patients with overweight or obesity who have prediabetes or T2D, given the known therapeutic effects of weight loss to lower glycemia, improve the lipid profile, reduce BP, prevent or delay the progression to T2D in patients with prediabetes, and decrease mechanical strain on the lower extremities (hips and knees).

Clinicians should evaluate patients for the risk, presence, and severity of complications, regardless of BMI, and these factors should determine treatment planning and further evaluation. Once assessed, clinicians can set therapeutic goals and select appropriate types and intensities of treatment that may help patients achieve their weight-loss goals and avert weight-related complications.

Key takeaways are as follows:

1. Rather than a BMI-centric approach for management of patients with overweight/obesity, the AACE has emphasised a complications-centric model which incorporates 3 disease stages:

• Stage 0 (elevated BMI with no obesity complications)
• Stage 1 (1 or 2 mild to moderate obesity complications)
• Stage 3 (>2 mild to moderate obesity complications, or ≥1 severe complication)

2. The primary clinical goal of weight-loss therapy is to prevent progression to T2D in patients with prediabetes and to achieve the target A1C in patients with T2D, in addition to improvements in lipids and BP. Patients should be periodically reassessed to determine if targets for improvement have been reached; if not, weight-loss therapy should be changed or intensified.
3. Weight-loss medications can be used to intensify therapy in combination with lifestyle therapy for all patients with a BMI ≥27 kg/m2 having complications and for patients with BMI ≥30 kg/m2 whether or not complications are present.
4. There are 8 FDA approved drugs that can be used as adjuncts to lifestyle therapy in patients with overweight or obesity.

• Diethylpropion, phendimetrazine, and phentermine for short-term use (≤3 months)
• Orlistat, phentermine/topiramate extended release (ER), lorcaserin, naltrexone ER/bupropion ER, and liraglutide 3 mg have been approved for long-term weight-reduction therapy

5. Consider Bariatric surgery for adult patients with a BMI ≥35 kg/m² and comorbidities, especially if therapeutic goals have not been reached using other modalitie

AACE/ACE comprehensive clinical practice guidelines for medical care of patients with obesity

These CPGs provide an evidence-based resource addressing rational approaches to the care of patients with obesity and an educational resource for the development of a comprehensive care plan for clinical endocrinologists and other health care professionals who care for patients with obesity.

Some of the important recommendations are:

1. All adults should be screened annually using a BMI measurement; in most populations a cut-off point of ≥25 kg/m² should be used to initiate further evaluation of overweight/obesity (Grade A). A cutoff point value of ≥23 kg/m² should be used in South Asian, Southeast Asian, and East Asian adults (Grade B).
2. BMI should be used to confirm an excessive degree of adiposity and to classify individuals as having overweight (BMI 25 to 29.9 kg/m²) or obesity (BMI ≥30 kg/m²), after taking into account age, gender, ethnicity, fluid status, and muscularity; therefore, clinical evaluation and judgment must be used when BMI is employed as the anthropometric indicator of excess adiposity, particularly in athletes and those with sarcopenia (Grade A).
3. When evaluating patients for adiposity related disease risk, waist circumference should be measured in all patients with BMI <35 kg/m². In many populations, a waist circumference cutoff point of ≥94 cm in men and ≥80 cm in women should be considered at risk and consistent with abdominal obesity (Grade A).
4. Screen obese/overweight patients for prediabetes and T2DM and evaluate for metabolic syndrome by assessing waist circumference, fasting glucose, A1C, blood pressure, and lipid panel, including triglycerides and HDL-c (Grade A)
5. Screen obese/overweight patients for active cardiovascular disease by history, physical examination, and with additional testing or expert referral based on cardiovascular disease risk status (Grade A).
6. Screening for non-alcoholic fatty liver disease should be performed in all patients with overweight or obesity, T2DM, or metabolic syndrome with liver function testing, followed by ultrasound or other imaging modality if transaminases are elevated (Grade B).
7. Premenopausal female patients with overweight or obesity and/or metabolic syndrome should be screened for PCOS by history and physical examination, women with overweight or obesity should be counseled when appropriate that they are at increased risk for infertility (Grade B).
8. Patients with overweight or obesity and with either metabolic syndrome or prediabetes, or patients identified to be at high risk of T2DM based on validated risk-staging paradigms, should be treated with lifestyle therapy that includes a reduced-calorie healthy meal plan and a physical activity program incorporating both aerobic and resistance exercise to prevent progression to diabetes (Grade A). The weight-loss goal should be 10% (Grade B).
9. Medication-assisted weight loss employing phentermine/topiramate ER, liraglutide 3 mg, or orlistat should be considered in patients at risk for future T2DM and should be used when needed to achieve 10% weight loss in conjunction with lifestyle therapy (Grade A).
10. Diabetes medications including metformin, acarbose, and thiazolidinediones can be considered in selected high-risk patients with prediabetes who are not successfully treated with lifestyle and weight-loss medications and who remain glucose intolerant (Grade A).
11. Diabetes medications that are associated with modest weight loss or are weight-neutral are preferable in patients with obesity and T2DM, although clinicians should not refrain from insulin or other medications when needed to achieve A1C targets (Grade A).
12. Patients with overweight or obesity and dyslipidemia (elevated triglycerides and reduced HDL-c) should be treated with lifestyle therapy to achieve 5 to 10% weight loss or more as needed to achieve therapeutic targets (Grade A).
13. Pharmacotherapy for overweight and obesity should be used only as an adjunct to lifestyle therapy and not alone (Grade A).
14. In selecting the optimal weight-loss medication for each patient, clinicians should consider differences in efficacy, side effects, cautions, and warnings that characterise medications approved for chronic management of obesity, and the presence of weight-related complications and medical history (Grade A).
15. Renin-angiotensin system inhibition therapy (angiotensin receptor blocker or angiotensin converting enzyme inhibitor) should be used as the first-line drug for BP control in patients with obesity (Grade A).
16. Combination anti HTN therapy with calcium channel blockers may be considered as second-tier treatment. blockers and thiazide diuretics may also be considered in some patients but can have adverse effects on metabolism; beta-blockers and alpha-blockers can promote weight gain (Grade A).