GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review.

Obesity and type 2 diabetes mellitus (T2DM) present major global health challenges, with an increasing prevalence worldwide. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a pivotal treatment option for both conditions, demonstrating efficacy in blood glucose management, weight reduction, cardiovascular disease prevention, and kidney health improvement. GLP-1, an incretin hormone, plays a crucial role in glucose metabolism and appetite regulation, influencing insulin secretion, insulin sensitivity, and gastric emptying. The therapeutic use of GLP-1RAs has evolved significantly, offering various formulations that provide different efficacy, routes of administration, and flexibility in dosing. These agents reduce HbA1c levels, facilitate weight loss, and exhibit cardiovascular protective effects, making them an integral component of T2DM and obesity management. This review will discuss the currently approved medication for T2DM and obesity, and will also highlight the advent of novel agents which are dual and triple hormonal agonists which represent the future direction of incretin-based therapy. Funding: National Institutes of HealthNIDDKU24 DK132733 (FCS), UE5 DK137285 (FCS), and P30 DK040561 (FCS).

Correlation of Anemia Due to Poor Iron Status With Obesity at King Fahad Medical City, Riyadh, Saudi Arabia.

Background Saudi Arabia has a high prevalence of chronic diseases such as obesity. Moreover, iron deficiency anemia (IDA) in developing countries is the most prevalent type of anemia. This study aims to assess the correlation between anemia related to poor iron status and obesity. Methods A cross-sectional observational study was conducted at the obesity center in King Fahad Medical City, Saudi Arabia, from April to September 2020. Two hundred and forty participants were needed to be included in the study. The data was gathered by utilizing a designed data collection form. Socio-demographic data, weight and height, questions related to the history of anemia, and gynecological data (for females) were collected. The data was analyzed using SPSS (Statistical Package for Social Science) version 28.0. Descriptive statistics were used to present numerical and categorical data and a Chi-square test was conducted to assess the correlation between categorical variables. Informed written consent was obtained from all participants and ethical approval was obtained from the Ethical Board Committee in King Fahad Medical City. Results The study included 240 participants. Two-thirds of the study population are females (64.6%), 66.7% are married, and 65.8% have obesity. Almost one-half of the study population (46%, N=128) was diagnosed with IDA with malnourishment being the most common reason for IDA (88.2%). The results indicated a correlation between obesity and the prevalence of IDA. The prevalence of IDA among participants with obesity (60.4%) was significantly higher compared to non-obese participants (39.5%), p=0.002. The study found that females and underweight individuals have a higher prevalence of IDA (p<0.001). Conclusion Results of the present study suggest that obesity could be associated with a risk of IDA. In addition, Saudi women could be more prone to IDA than men. Further prospective controlled studies among diverse populations in Saudi Arabia including laboratory assessment of inflammatory markers and iron status are required to better understand the correlation between obesity and IDA.

Global Impact of Obesity.

The prevalence of preobesity and obesity is rising globally, multiple epidemiologic studies have identified preobesity and obesity as predisposing factors to a number of noncommunicable diseases including type 2 diabetes (T2DM), cardiovascular disease (CVD), and cancer. In this review, we discuss the epidemiology of obesity in both children and adults in different regions of the world. We also explore the impact of obesity as a disease not only on physical and mental health but also its economic impact.

Clinical effectiveness of Liraglutide 3.0 mg and impact of weight loss in improving obesity-related comorbid conditions in King Fahad Medical City, Kingdom of Saudi Arabia: A real-world experience.

Obesity has emerged as one of the most challenging worldwide problems and, if left untreated, can lead to major illnesses and consequences that can impair patients' health The study's objective was to evaluate the effectiveness of Liraglutide 3.0 mg in inducing weight loss and to assess the improvement of obesity-related comorbid conditions among people living with obesity (PwO) in the Kingdom of Saudi Arabia (KSA). A retrospective cohort review of PwO with or without diabetes and taking Liraglutide 3.0 mg in combination with diet and exercise for weight management was performed and evaluated at King Fahad Medical City, Riyadh, KSA. We collected patient data from electronic medical records for different parameters. The side effects were not recorded. A cohort of 399 patients who used Liraglutide 3.0 mg for 6 months was included in the study. At baseline, the mean age of the cohort was 46.4 (±12.1) years, mean BMI was 40.4 (±7.7) kg/m2 and most patients (74.4%) were women. Their mean average weight loss was 6.5 (±9.5) kg; p < .001. In the entire cohort, 52.6% of subjects had lost ≥5% of their bodyweight, 27.8% of subjects had lost ≥10%, and 11.3% of subjects had lost ≥15% of their bodyweight. There was a significant reduction in HbA1c by 0.5% (p < .0001) at 6 months of the treatment. Liraglutide 3.0 mg treatment did not affect systolic blood pressure and alanine transferase. Liraglutide 3.0 mg resulted in clinically significant weight loss with better glycaemic control, confirming the drug's effectiveness in the real-world evidence setting.

Changing trends in liver transplantation indications in Saudi Arabia: from hepatitis C virus infection to nonalcoholic fatty liver disease.

BACKGROUND: Several trend analyses on liver transplantation (LT) indications have been published in the U.S. and in other countries, but there are limited data on LT indication trends in Saudi Arabia (SA), especially since the availability of direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV). This study aimed to analyze trends in the frequency of LT indications among LT recipients in SA over a 19-year period and examine associations between etiologic-specific trends and clinicodemographic characteristics. METHODS: This retrospective study analyzed clinical and surgical data of adult patients (n = 1009) who underwent LT at the King Faisal Specialist Hospital & Research Center (Riyadh, SA) between 2001 and 2019. Spearman's rank correlation, Poisson regression, and Joinpoint regression analysis were employed to assess changes in LT etiologic trends. RESULTS: In the first period (2001-2010), the main LT indications were HCV (41.9%) and hepatitis B virus (HBV) (21.1%), but nonalcoholic steatohepatitis (NASH) (29.7%) surpassed HCV (23.7%) as the leading LT indication in the second period (2011-2019); and the trends were significant in correlation analyses [incidence rate ratio (IRR) = 1.09 (1.06-1.13) for NASH; IRR = 0.93 (0.91-0.95) for HCV]. In the Joinpoint regression analysis, increases in NASH from 2006 to 2012 (+ 32.1%) were statistically significant, as were the decreases in HCV from 2004 to 2007 (- 19.6%) and from 2010 to 2019 (- 12.1%). Similar patterns were observed in LT etiological comparisons before and after the availability of DAAs and within hepatocellular carcinoma stratifications. CONCLUSIONS: Trends in the epidemiology of LT indications among LT recipients in SA have changed over a 19-year period. Most notably, NASH has eclipsed HCV in the country due to the effective treatment strategies for HCV. These trends in NASH now need an aggressive public health response to minimize and avert future onset of additional clinical and economic strains on health care systems and LT centers in SA.

Effects of addictive-like eating behaviors on weight loss with behavioral obesity treatment.

To examine the relationship between food cravings and food addiction as defined by the Yale Food Addiction Scale (YFAS) and to assess the effects of these variables on weight loss during a 14-week group lifestyle modification program. Data were from 178 participants who were prescribed a 1000-1200 kcal/day portion-controlled diet and provided with weekly group lifestyle modification sessions. Participants completed the Food Craving Inventory and YFAS pre- and post-treatment. Weight was measured weekly. Participants with YFAS-defined food addiction (6.7%) reported more frequent overall food cravings relative to those without food addiction. More frequent food cravings at baseline were associated with less weight loss over the 14 weeks. Analyzed categorically, participants in the highest tertile of baseline food cravings lost 7.6 ± 0.5% of initial weight, which was significantly less compared to those in the lowest tertile who lost 9.1 ± 0.5%. Percent weight loss did not differ significantly between participants with YFAS-defined food addiction (6.5 ± 1.2%) and those who did not meet criteria (8.6 ± 0.3%). Addictive-like eating behaviors significantly declined from pre- to post-treatment. Participants with frequent food cravings lost less weight than their peers. Targeted interventions for food cravings could improve weight loss in these individuals. Few participants met YFAS-defined criteria for food addiction. Addictive-like eating behaviors tended to decline during behavioral weight loss, but neither baseline nor change in YFAS scores predicted weight loss.

"Last Supper" Predicts Greater Weight Loss Early in Obesity Treatment, but Not Enough to Offset Initial Gains.

Background: Many participants experience clinically significant fluctuations in weight before beginning a behavioral weight loss program. Pre-treatment weight gain, often referred to as the "last supper" effect, may limit total weight loss from the time of the pre-treatment screening visit and could be an indicator that a participant will respond poorly to behavioral intervention. Methods: Data were from the weight loss phase of a two-phase weight loss maintenance trial, in which 178 participants with obesity (screening BMI = 40.5 ± 6.0 kg/m2, 87.6% female; 71.3% black) were provided with a 14 week lifestyle intervention that included a meal replacement diet. Participants were categorized as having gained >1.15%, remained weight stable, or lost >1.15% of initial weight between the pre-treatment screening visit and the first treatment session (48.7 ± 29.4 days). We first examined whether the weight change groups differed in baseline eating characteristics (e.g., emotional eating, self-regulation, craving frequency) using one-way ANCOVAs. Linear mixed models were then used to compare weight change groups on total weight loss from the screening visit to week 14 and in-treatment weight loss from weeks 1 to 14. Results: Nearly half of the sample (48.9%) gained >1.15% of initial weight during the pre-treatment period (+2.5 ± 1.2%); 41.0% remained weight stable (+0.2 ± 0.6%); and 10.1% lost >1.15% of initial weight (-2.2 ± 0.9%). There were no significant differences between the groups in baseline eating characteristics. As measured from the screening weight, the weight-gain group had a lower total loss of 6.8%, compared to 7.8% in the weight stable group (p = 0.02) and 9.0% in the weight-loss group (p = 0.003). The weight-gain group lost more weight in the first 4 weeks of treatment, but in-treatment losses did not differ among the groups at week 14. Conclusion: Pre-treatment weight gain was not an indicator of a poor response to a behavioral weight loss intervention and was associated with greater weight loss early in treatment. However, weight gain during the pre-treatment period may limit the total weight loss that participants achieve from the time that they first enroll in a weight loss program.

Short- and Long-Term Changes in Health-Related Quality of Life with Weight Loss: Results from a Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to determine the effects of weight loss and weight loss maintenance (WLM) on weight-specific health-related quality of life in a 66-week trial. METHODS: Adults with obesity (N = 137, 86.1% female, 68.6% black, mean age = 46.1 years) who had lost ≥ 5% of initial weight in a 14-week intensive lifestyle intervention/low-calorie diet (LCD) program were randomly assigned to lorcaserin or placebo for an additional 52-week WLM program. The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scale (including five subscales), Patient Health Questionnaire-9 (depression), and Perceived Stress Scale were administered at the start of the 14-week LCD program, randomization, and week 52 of the randomized controlled trial (i.e., 66 weeks total). RESULTS: Significant improvements in all outcomes, except weight-related public distress, were found following the 14-week LCD program (P values < 0.05). Improvements were largely maintained during the 52-week randomized controlled trial, despite weight regain of 2.0 to 2.5 kg across treatment groups. Participants who lost ≥ 10% of initial weight achieved greater improvements in physical function, self-esteem, sexual life, and the IWQOL-Lite total score than those who lost < 5% and did not differ from those who lost 5% to 9.9%. CONCLUSIONS: Improvements in weight-specific health-related quality of life were achieved with moderate weight loss and were sustained during WLM.

A Randomized Trial of Lorcaserin and Lifestyle Counseling for Maintaining Weight Loss Achieved with a Low-Calorie Diet.

OBJECTIVE: Improving the maintenance of lost weight remains a critical challenge, which can be addressed by long-term behavioral and/or pharmacological interventions. METHODS: This study investigated the efficacy of combined behavioral and pharmacological treatment in facilitating weight loss maintenance (WLM) in 137 adults (86.1% female; 68.6% black; BMI = 37.0 ± 5.6 kg/m2 ) who had lost ≥ 5% of initial weight during a 14-week low-calorie diet (LCD) program (mean = 9.3 ± 2.9%). Participants were randomly assigned to lorcaserin (10 mg twice a day) or placebo and were provided 16 group WLM counseling sessions over 52 weeks. RESULTS: At 24 weeks post randomization, more lorcaserin-treated than placebo-treated participants maintained a ≥ 5% loss (73.9% vs. 57.4%; P = 0.033), and the lorcaserin-treated participants lost an additional 2.4 ± 0.8 kg versus a 0.6 ± 0.8 kg gain for placebo (P = 0.010). However, at week 52, groups did not differ on either co-primary outcome; 55.1% and 42.6%, respectively, maintained ≥ 5% loss (P = 0.110), with gains from randomization of 2.0 ± 0.8 kg and 2.5 ± 0.8 kg (P = 0.630), respectively. From the start of the LCD, groups maintained reductions of 7.8% and 6.6%, respectively (P = 0.318). CONCLUSIONS: Combined behavioral and pharmacological treatment produced clinically meaningful long-term weight loss in this group of predominantly black participants. Lorcaserin initially improved upon weight loss achieved with WLM counseling, but this advantage was not maintained at 1 year.

Lorcaserin plus lifestyle modification for weight loss maintenance: Rationale and design for a randomized controlled trial.

BACKGROUND/AIMS: Few studies have examined the efficacy of recently approved medications for chronic weight management in facilitating the maintenance of lost weight. This paper provides an overview of the design and rationale for a trial investigating whether lorcaserin, when combined with behavioral weight loss maintenance sessions (WLM), will facilitate the maintenance of losses of ≥5% of initial weight. METHODS: In this two-phase trial, participants with obesity will enroll in a 14-week run-in diet program consisting of weekly group lifestyle modification sessions and a 1000-1200kcal/d meal replacement diet. Participants who complete this weight induction phase and lose at least 5% of initial weight will then be randomized to 52weeks of WLM plus lorcaserin or WLM plus placebo. We hypothesize that at 52weeks post randomization, participants assigned to WLM plus lorcaserin will achieve significantly better maintenance of the prior 5% weight loss. RESULTS: We will recruit 182 adults with obesity to participate in the diet run-in, 136 of whom (75%) are expected to become eligible for the randomized controlled trial. Co-primary outcomes include the percentage of participants who maintain a loss of at least 5% of initial weight at week 52 and change in weight (kg) from randomization to week 52. CONCLUSIONS: This two-phase design will allow us to determine the potential efficacy of chronic weight management using lorcaserin for maintaining initial losses of at least 5% body weight, induced by the use of a structured meal-replacement diet. This combined approach holds promise of achieving larger long-term weight losses. CLINICAL TRIAL REGISTRATION: NCT02388568 on ClinicalTrials.gov.

Association between weight bias internalization and metabolic syndrome among treatment-seeking individuals with obesity.

OBJECTIVE: Weight stigma is a chronic stressor that may increase cardiometabolic risk. Some individuals with obesity self-stigmatize (i.e., weight bias internalization, WBI). No study to date has examined whether WBI is associated with metabolic syndrome. METHODS: Blood pressure, waist circumference, and fasting glucose, triglycerides, and high-density lipoprotein cholesterol were measured at baseline in 178 adults with obesity enrolled in a weight-loss trial. Medication use for hypertension, dyslipidemia, and prediabetes was included in criteria for metabolic syndrome. One hundred fifty-nine participants (88.1% female, 67.3% black, mean BMI = 41.1 kg/m2 ) completed the Weight Bias Internalization Scale and Patient Health Questionnaire (PHQ-9, to assess depressive symptoms). Odds ratios and partial correlations were calculated adjusting for demographics, BMI, and PHQ-9 scores. RESULTS: Fifty-one participants (32.1%) met criteria for metabolic syndrome. Odds of meeting criteria for metabolic syndrome were greater among participants with higher WBI, but not when controlling for all covariates (OR = 1.46, 95% CI = 1.00-2.13, P = 0.052). Higher WBI predicted greater odds of having high triglycerides (OR = 1.88, 95% CI = 1.14-3.09, P = 0.043). Analyzed categorically, high (vs. low) WBI predicted greater odds of metabolic syndrome and high triglycerides (Ps < 0.05). CONCLUSIONS: Individuals with obesity who self-stigmatize may have heightened cardiometabolic risk. Biological and behavioral pathways linking WBI and metabolic syndrome require further exploration.

The utility of weight loss medications after bariatric surgery for weight regain or inadequate weight loss: A multi-center study.

BACKGROUND: Patients who undergo bariatric surgery often have inadequate weight loss or weight regain. OBJECTIVES: We sought to discern the utility of weight loss pharmacotherapy as an adjunct to bariatric surgery in patients with inadequate weight loss or weight regain. SETTING: Two academic medical centers. METHODS: We completed a retrospective study to identify patients who had undergone bariatric surgery in the form of a Roux-en-Y gastric bypass (RYGB) or a sleeve gastrectomy from 2000-2014. From this cohort, we identified patients who were placed on weight loss pharmacotherapy postoperatively for inadequate weight loss or weight regain. We extracted key demographic data, medical history, and examined weight loss in response to surgery and after the initiation of weight loss pharmacotherapy. RESULTS: A total of 319 patients (RYGB = 258; sleeve gastrectomy = 61) met inclusion criteria for analysis. More than half (54%; n = 172) of all study patients lost≥5% (7.2 to 195.2 lbs) of their total weight with medications after surgery. There were several high responders with 30.3% of patients (n = 96) and 15% (n = 49) losing≥10% (16.7 to 195.2 lbs) and≥15% (25 to 195.2 lbs) of their total weight, respectively, Topiramate was the only medication that demonstrated a statistically significant response for weight loss with patients being twice as likely to lose at least 10% of their weight when placed on this medication (odds ratio = 1.9; P = .018). Regardless of the postoperative body mass index, patients who underwent RYGB were significantly more likely to lose≥5% of their total weight with the aid of weight loss medications. CONCLUSIONS: Weight loss pharmacotherapy serves as a useful adjunct to bariatric surgery in patients with inadequate weight loss or weight regain.

Combination phentermine and topiramate extended release in the management of obesity.

INTRODUCTION: Losing ≥ 5% of initial weight improves quality of life and risk factors for cardiovascular disease (CVD) in obese individuals. Lifestyle modification, the cornerstone of weight reduction, may be complemented by pharmacotherapy. In 2012, the FDA approved the combination of phentermine and topiramate extended release (ER) for chronic weight management, as an adjunct to lifestyle modification. AREAS COVERED: This review examines the safety and efficacy of phentermine-topiramate ER, as determined by randomized controlled trials (RCTs). A preliminary study confirmed the benefit of combining the two medications for improving weight loss and reducing adverse effects, as compared to using equivalent-dose monotherapy alone. EXPERT OPINION: Across RCTs, groups prescribed phentermine 15 mg/topiramate ER 92 mg lost an average of 10% of initial weight, ∼ 8% more than placebo and 2% more than phentermine 7.5 mg/topiramate 46 mg. Weight loss reduced the risk of developing type 2 diabetes and improved CVD risk factors. Phentermine-topiramate ER, however, was associated with increased heart rate, the clinical significance of which is being investigated in an FDA-required CVD outcomes study. The medication also must be used with caution in women of child-bearing age because of an increased risk to infants of oral cleft.

Effects of a 2-year behavioral weight loss intervention on sleep and mood in obese individuals treated in primary care practice.

OBJECTIVE: To examine the effect of weight loss on sleep duration, sleep quality, and mood in 390 obese men and women who received one of three behavioral weight loss interventions in the Practice-based Opportunities for Weight Reduction trial at the University of Pennsylvania (POWER-UP). METHODS: Sleep duration and quality were assessed at baseline and months 6 and 24 by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and mood by the Patient Health Questionnaire-8 (PHQ-8). Changes in sleep and mood were examined according to treatment group and based on participants' having lost ≥5% of initial weight vs. <5%. RESULTS: There were few significant differences between treatment groups in changes in sleep or mood. At month 6, however, mean (±SD) min of sleep increased significantly more in participants who lost ≥5% vs. <5% (21.6 ± 7.2 vs. 1.2 ± 6.0 min, P = 0.0031). PSQI total scores similarly improved (declined) more in those who lost ≥5% vs. <5% (-1.2 ± 0.2 vs. -0.4 ± 0.2, P < 0.001), as did PHQ-8 scores (-2.5 ± 0.4 vs. -0.1 ± 0.3, P < 0.0001). At month 24, only the differences in mood remained statistically significant (P < 0.05). CONCLUSION: Losing ≥5% of initial weight was associated with short-term improvements in sleep duration and sleep quality, as well as favorable short- and long-term changes in mood.