Trends in Non-pharmacologic Treatment of Obesity

Educational Objectives

The goal of this program is to improve management of obesity with bariatric surgery. After hearing and assimilating this program, the clinician will be better able to:

1. Counsel patients on nutrition and exercise as part of an individualized and patient-centered approach to treating obesity.
2. Improve the rate of diabetes remission in patients undergoing bariatric surgery (BS) through early intervention.
3. Prevent excessive weight regain after BS.

Summary

Obesity in the United States (US): rates of obesity and severe obesity in the US are rising, and current strategies are ineffective; diets deficient in fruits and vegetables and sedentary lifestyles contribute to obesity; exercise is a tool for weight maintenance, not weight loss (WL); healthy behavior may be confused with WL behavior; providers should have conversations on weight management with patients before severe obesity develops

Physical activity: calorie reduction and increased exercise may improve cardiovascular function but does not induce WL; strength training in aging adults produces direct and indirect health benefits (eg, maintenance of lean body mass, increased metabolic rate, reduced risk for weight regain)

Dietary studies: studies show that consistency is more important than macronutrient composition for WL; the effects of macronutrient-restricted diets on weight and blood pressure are not durable at 6 mo; Hall et al (2019) — randomized participants into groups receiving ultra-processed food (eg, muffin, packaged pastry) or unprocessed foods that require more chewing (eg, kale salad); participants in the ultra-processed food group consumed ≈500 kcal/day more than the unprocessed group; the additional calories came mostly from fats and carbohydrates; ultra-processed foods may be consumed more quickly; the quality of calories, the order in which food (based on its macronutrient profile) is consumed, and the length of a meal may be important; Shukla et al (2017) — found that consuming carbohydrates first increased levels of ghrelin (hormone that increases hunger), suggesting that ingestion of carbohydrates last may be effective for WL; intermittent fasting — randomized studies have found that it is not effective for WL

Patient-centered approach: providers may help patients objectively assess their own eating behavior; effective and evidence-based approaches to treating obesity varies based on each patient; evidence indicates that an automated approach to individualized challenges is not effective; a more patient-centered approach is needed

Health benefits other than WL: metabolic (eg, lower fasting glucose) and cardiovascular benefits of intermittent fasting are being studied; patients should be encouraged to continue pursuing healthy behaviors (eg, physical activity) that may not directly cause WL

Very low calorie diets (VLCDs): the DiRECT trial (Lean et al, 2019) assessed diabetes remission in patients receiving a meal replacement program (consisting of 825 kcal/day) for 3 mo; the average WL was ≈10 kg; larger amount of WL was associated with a higher diabetes remission rate (DRR), ie, DRR at 2 yr was ≥70% in patients with WL >15 kg; VLCDs are safe interventions for multiple conditions (eg, WL, diabetes, fatty liver disease) with appropriate risk stratification and recommended follow-up care; because insulin resistance is caused by multiple mechanisms, producing meaningful outcomes depends on tailoring interventions to specific conditions

Setting goals for weight reduction: a long-term goal for WL is important; for every 5 body mass index points above a healthy range, mortality increases by ≈30%; in patients with diabetes, a WL of ≥10% results in reduction in cardiovascular events of ≈20%; for patients with diabetes and fatty liver disease, WL of 10% is a meaningful objective; nonpharmacologic therapies are an option for patients prescribed anti-obesity medications (AOM) other than semaglutide (eg, liraglutide) that do not reach this goal

Superabsorbent hydrogel (Gelesis100): a medical device (ie, capsule) that is administered orally and expands to occupy space in the stomach when ingested with water prior to meals, inducing satiety; patients with BMI from 25 to 40 are eligible; the GLOW trial (Greenway et al, 2019) found that participants who received superabsorbent hydrogel achieved greater WL vs those who received placebo (≈6.4% vs≈4.4%); WL of ≥10% was achieved by ≈27% of participants in the intervention group; patients with hyperglycemia derived more WL benefits; reduction in markers for insulin resistance and fatty liver disease was also observed

Bariatric surgery (BS): an evidence-based and effective treatment for obesity, but it is performed in <1% of eligible patients; complication rates for BS are comparable to those of laparoscopic cholecystectomy for most patients; patients with multiple comorbidities and severe obesity are at higher risk for complications but often undergo other elective surgeries (eg, joint replacement) with similar or higher risks; BS may improve long-term health and quality of life; sleeve gastrectomy (GS) (the most common BS performed in the US), was found to be effective for WL in ≈70% of patients in randomized control trials at 2 yr; other BS procedures include gastric bypass (GB) and biliopancreatic diversion (BPD)

Cardiometabolic benefits of BS: fatty liver disease and hypertension resolves in approximately two-thirds of patients; hemoglobin A_1C (HbA_1C) decreases by ≈2 points; lipid and C-reactive protein levels improve

Effects of BS on diabetes: 5-yr data from the STAMPEDE trial (Schauer et al, 2017) and Mingrone et al (2015) found a diabetes remission rate (DRR) of ≈23% with SG, 31% to 37% with GB, and ≈63% with BPD; reduction in HbA_lc was greatest with BPD; BS treats obesity and reduces HbA_lc; 10-yr data show similar benefits; HbA_1c was <7% in patients who experienced recidivism in their diabetes; patients who underwent BS had fewer diabetes-related complications compared with those who received medical therapy; Swedish study — found DRR of ≈90% at 2 yr and ≈60% at 10 yr for patients with diabetes duration of <1 yr; DRR was ≈40% at 2 yr and ≈10% at 10 yr for patients with diabetes duration of ≥4 yr; physiology may not be able to rebound if diabetes intervention is delayed; increased chance of diabetes remission is predicted by shorter duration of diabetes, successful preoperative control, age, not receiving insulin therapy, and smaller waist circumference; WL of ≈20% is the threshold for significant remission of diabetes (particularly for patients receiving insulin therapy); clinical data show reduction in all-cause mortality and composite major adverse cardiovascular events outcomes in patients with diabetes who underwent BS; procedure selection — patients who underwent Roux-en-Y GB (RYGB) had greater reduction in HbA_1c, more WL, better cardiovascular outcomes, and less nephropathy compared with patients who underwent SG

Effects of BS on cardiovascular diseases: clinical data indicate improvement in all-cause mortality and survival and reduction in hospitalization for heart failure in patients with pre-existing cardiovascular diseases; BS may be used as a tool to reduce cardiovascular risk

Life expectancy (LE) and BS: LE of people with severe obesity is reduced by 8.5 yr compared with the nonobese population; BS may increase LE by 3 yr

Endobariatric procedures (EBPs) for obesity: endoscopic sleeve gastroplasty (ESG) — reduces gastric volume by endoscopic suturing; EBP is typically performed in conjunction with other treatments (eg, VLCD, AOM); ≈80% of patients maintained WL of ≈10% after 5 yr; gastric balloons — approved for 6-mo duration in the stomach; rupture of the device may be fatal; other options — include endoscopically delivered intragastric device (TransPyloric Shuttle), percutaneous gastrostomy (AspireAssist), and duodenal-jejunal bypass sleeve; traditional laparoscopic sleeve gastrectomy (TLSG) vs ESG — the speaker prefers TLSG because it produces consistent WL and is more often covered by insurance; patients who undergo ESG may experience anxiety because the mechanical restriction prevents a sense of satiety; AOM are often used concomitantly with ESG; TLSG causes a greater reduction in ghrelin levels compared with ESG; postprandial increase in glucagon-like peptide 1 (GLP-1) is absent in individuals who undergo ESG

Self-assembling magnets: an emerging therapy; induce pressure necrosis to create a bypass between the upper small intestine and lower intestine; WL is modest, but reduction in HbA_1c is promising

Weight regain after BS: patients should be informed that weight regain is expected after BS and is not a sign of failure; may be caused by anatomic, hormonal, and behavioral factors; patients are well served by development of an integrated program focused on healthy, sustainable, and evidence-based habits for nutrition, activity, and behavior; pharmacotherapy is effective when judiciously used; bariatric revisions combined with pharmacotherapy may be effective in moderating weight regain; topiramate and phentermine may be used to manage weight regain and optimize weight reduction after BS; GLP-1 — based polypharmacy regimens for treatment of obesity are often more effective than regimens without GLP-1 receptor agonists

Endoscopic revision of BS: endoscopic revision of RYGB (eg, with laser repair, suturing) addresses gradual stretching of gastrojejunal stoma and may result in WL of ≥10%; incorporating AOM may increase WL further; GB after SG produces WL of ≈10% at ≥3 yr; health benefits extend beyond absolute weight reduction; endoscopic revision of SG (ie, re-sleeve) results in WL of ≈15%; GLP-1 — based medications are more effective after re-sleeve

Readings

Changela K, Ofori E, Duddempudi S, Anand S, Singhal S. Peroral endoscopic reduction of dilated gastrojejunal anastomosis after bariatric surgery: techniques and efficacy. World J Gastrointest Endosc. 2016; 8(4):239-243. doi:10.4253/wjge.v8.i4.239; English WJ, DeMaria EJ, Hutter MM, et al. American Society for Metabolic and Bariatric Surgery 2018 estimate of metabolic and bariatric procedures performed in the United States. Surg Obes Relat Dis. 2020; 16(4):457-463. doi:10.1016/j.soard.2019.12.022; Freedhoff Y, Hall KD. Weight loss diet studies: we need help not hype. Lancet. 2016; 388(10047):849-851. doi:10.1016/S0140-6736(16)31338-1; Greenway FL, Aronne LJ, Raben A, et al. A randomized, double-blind, placebo-controlled study of Gelesis100: a novel nonsystemic oral hydrogel for weight loss [published correction appears in Obesity (Silver Spring). 2019 Apr; 27(4):679] [published correction appears in Obesity (Silver Spring). 2019 Jul; 27(7):1210]. Obesity (Silver Spring). 2019; 27(2):205-216. doi:10.1002/oby.22347; Hall KD, Ayuketah A, Brychta R, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake [published correction appears in Cell Metab. 2019 Jul 2; 30(1):226] [published correction appears in Cell Metab. 2020 Oct 6; 32(4):690]. Cell Metab. 2019; 30(1):67-77.e3. doi:10.1016/j.cmet.2019.05.008; Hutch CR, Sandoval D. The role of GLP-1 in the metabolic success of bariatric surgery. Endocrinology. 2017;158(12):4139-4151. doi:10.1210/en.2017-00564; Lean MEJ, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019; 7(5):344-355. doi:10.1016/S2213-8587(19)30068-0-3; Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2015; 386(9997):964-973. doi:10.1016/S0140-6736(15)00075-6; Mingrone G, Panunzi S, De Gaetano A, et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2021; 397(10271):293-304. doi:10.1016/S0140-6736(20)32649-0; Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes - 5-Year Outcomes. N Engl J Med. 2017; 376(7):641-651. doi:10.1056/NEJMoa1600869; Seo J, Jung WS, Kim SW, Kim J, Park HY, Lim K. Resistance Training Enhances Muscle Function and Hemorheological Properties in Middle-aged Obese Women. FASEB J. 2022;36 Suppl 1:10.1096/fasebj.2022.36.S1.R4384. doi:10.1096/fasebj.2022.36.S1.R4384; Shukla AP, Andono J, Touhamy SH, et al. Carbohydrate-last meal pattern lowers postprandial glucose and insulin excursions in type 2 diabetes. BMJ Open Diabetes Res Care. 2017; 5(1):e000440. Published 2017 Sep 14. doi:10.1136/bmjdrc-2017-000440.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Almandoz was recorded at the Georgia Society of Endocrinology 2022 Annual Meeting, held February 4-6, 2022, in Atlanta, GA, and presented by the Georgia Society of Endocrinology. For more information about upcoming CME activities from this presenter, please visit https://endoconnection.com/ga/meetings. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

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