Benefits Of Weight Loss Research Articles

Short-Term Weight Loss Decreased the Risk of Chronic Kidney Disease in Incident NAFLD Participants: A Prospective Cohort

Background: Weight loss-centered lifestyle remains a first-line intervention for non-alcoholic fatty liver disease (NAFLD). However, whether weight loss benefits adverse kidney outcomes is uncertain. Therefore, we aimed to investigate baseline and changes in obesity measures on chronic kidney disease (CKD) risks after NAFLD occurrence. Methods: We enrolled 10311 adult men with newly diagnosed NAFLD and without CKD in the Kailuan cohort in 2006–2013. The Fine and Gray competing risk regression model was used to compare the advanced CKD risk in NAFLD with different baseline or trajectories in obesity measures after 1–4 years of NAFLD diagnosis. Findings: During a median follow-up of ten years, baseline body mass index (BMI), waist circumference (WC), and waist-hip ratio (WHR) were not observed associated with CKD development for incident NAFLD subjects. Maintaining WC or WHR, or transition from obese to nonobese determined by the BMI decreased a 31% [95% confidence interval (CI): 0·51–0·93], 34% (95% CI: 0·45–0·95), and 38% (95% CI: 0·40–0·96) of the CKD hazard compared to the corresponding constantly normal subgroup, respectively. In addition, NAFLD individuals with ≥10% weight loss (HR=0 · 58, 95%CI: 0·34–0·97) and 7·0%–9·9% weight loss (HR=0·53, 95% CI: 0·28–0·99) had a lower risk for CKD than those with weight change ± 4·9%. Interpretation: Short-term weight loss or keeping WC or WHR was associated with a lower risk of CKD for patients with incident NAFLD. Our findings, if verified by more research with long-term prospective cohort study, suggest the importance of monitoring WC, WHR, and weight for newly diagnosed NAFLD patients' management. Funding: This work was supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-3-001 and 2019-I2M-2-007). Declaration of Interest: We declare that we have no conflicts of interest. Ethical Approval: This study was approved by the Ethics Committees of the Kailuan General Hospital and the Institute of Basic Medical Sciences Chinese Academy of Medical Sciences.

Pre-specified Weight Loss Before Bariatric Surgery and Postoperative Outcomes.

Bariatric surgery is increasing exponentially to address the steep rise in the prevalence of severe obesity. Most centers require pre-specified preoperative weight loss before allowing patients to receive surgery. We examined the current evidence surrounding the potential benefits of this requirement on postoperative outcomes. We reviewed the current literature by conducting a multistage advance electronic search in Ovid®/MEDLINE® and PubMed for publications indexed after 2008 reporting preoperative weight loss and postoperative outcomes. Thirteen original publications, three randomized control trials (RCT), and five systematic reviews that met inclusion criteria were included. These were analyzed with regards to weight loss before surgery and postoperative outcomes. There were varied reports regarding the significant effect of preoperative weight loss. Six of the original articles (50%) did not identify a significant difference in the outcome while two of the RCT (essentially the same patient population, started in 2007 and reanalyzed in 2009) demonstrated some advantage. A later RCT (2012) did not show any advantage, albeit in the short term. The results of the systematic reviews, some with heterogenic designs, show no conclusive evidence that weight loss before surgery conferred improved postoperative outcomes. There is not enough high-quality evidence to back up the requirement of pre-specified preoperative weight loss before receiving surgery. Further validation of the possible benefits of pre-specified preoperative weight loss may need to be carried out.

Zumba®, Fat Mass and Maximum Oxygen Consumption: A Systematic Review and Meta-Analysis.

Background and objectives: Obesity or overweight is associated with many health risk factors and preventable mortality. Even people with normal weight and without history of obesity or overweight should avoid weight gain to reduce health risks factors. In this regard Latin aerobic dances involved in Zumba® practice make this modality motivating for people. Apart from weight loss and VO2peak benefits, Zumba practice is also interesting by the increase in adherence which can also avoid weight regain. The aim was to systematically review the scientific literature about the effects of any randomized intervention of Zumba® practice on total fat mass (%) and maximum oxygen consumption (VO2peak), besides establishing directions for the clinical practice. Evidence acquisition: Two systematic searches were conducted in two electronic databases following the PRISMA guidelines. The eligibility criteria were (a) outcomes: body mass or VO2peak data including mean and standard deviation (SD) before and after Zumba® intervention, (b) study design: randomized controlled trial (RCT) and (c) language: English. GRADE guidelines were used to assess the quality of evidence. A meta-analysis was performed to determine mean differences. Nine and four studies were selected for fat mass percentage and VO2peak in the systematic review, respectively. However, only eight studies for fat mass percentage and three for VO2peak could be included in the meta-analysis. Evidence synthesis: The overall standardized mean difference for fat mass was −0.25 with a 95% CI from −0.67 to 0.16 with a p-value of 0.69, with large heterogeneity. On the other hand, the overall effect size for VO2peak was 0.53 (95% CI from 0.04 to 1.02 with a p-value of 0.03) with large heterogeneity. Conclusions: Based on the evidence, we cannot conclude that Zumba® is effective at reducing body mass but it may improve VO2peak. However, the limited number of studies that met the inclusion criteria makes it too early to reach a definite conclusion, so more research is needed.

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium-glucose co-transporter inhibitors with insulin for treatment of type 1 diabetes (updated October 2020)

Dapagliflozin (sodium-glucose co-transporter (SGLT-2) inhibitor) and sotagliflozin (SGLT-1/2 inhibitor) are two of the drugs of the SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with body mass index ≥27 kg/m2. Dapagliflozin is licensed in the UK for use in the NHS while sotagliflozin may be available in future. These and possibly other SGLT inhibitors may be increasingly used in people with type 1 diabetes as new licences are obtained. These drugs have the potential to improve glycaemic control in people with type 1 diabetes with the added benefit of weight loss, better control of blood pressure and more time in optimal glucose range. However, SGLT inhibitors are associated with a higher incidence of diabetic ketoacidosis without significant hyperglycaemia. The present ABCD/Diabetes UK joint updated position statement is to guide people with type 1 diabetes and clinicians using these drugs to help mitigate this risk and other potential complications. Particularly, caution needs to be exercised in people who are at risk of diabetic ketoacidosis due to low calorie diets, illnesses, injuries, starvation, excessive exercise, excessive alcohol consumption and reduced insulin administration, among other precipitating factors for diabetic ketoacidosis.

A critical review of weight loss recommendations before total knee arthroplasty.

Increased infection risk after total knee arthroplasty (TKA) in patients with a higher body mass index (BMI), particularly a BMI ≥40kg/m2, suggests that BMI reduction (through weight loss) prior to TKA may be important. However, the impact of weight loss on TKA risk reduction is unclear. Furthermore, weight loss could have detrimental consequences with respect to muscle loss and development of sarcopenic obesity, whereby a potential weight loss paradox in adults with advanced knee OA and obesity may be present. Using a critical review approach, we examined the current evidence supporting weight loss in adults with obesity and advanced knee osteoarthritis (OA). We focused on three key areas: (1) TKA complication risk with severe obesity compared to obesity (BMI ≥40kg/m2 versus 30.0-39.9kg/m2); (2) weight loss recommendations for individuals with advanced knee OA; and (3) TKA outcomes after pre-surgical weight loss. Medline and CINAHL databases were examined from Jan 2010 to May 2020 to identify high-level and/or clinically-influential evidence (systematic reviews, meta-analyses and clinical practice guidelines). The literature does not show a clear relationship between weight loss and reduction in TKA complications, and no indication that a patients' individual risk is lowered by reducing their BMI from a threshold of ≥40kg/m2 to ≤39.9kg/m2. Studies that have found a benefit of weight loss for knee OA have not included patients with higher BMIs (≥40kg/m2) or more advanced knee OA. Furthermore, there is unclear evidence of a benefit of pre-surgical weight loss on TKA outcomes. These are important evidence gaps, suggesting that recommendations for BMI reduction prior to TKA should be tempered by the current uncertainty in the literature. Evidence to support a benefit of weight loss prior to TKA is lacking. Until knowledge gaps are clarified, it is recommended that practitioners consider individual patient needs and risk before recommending weight loss (and therefore BMI reduction).

Liraglutide and semaglutide: Pooled post hoc analysis to evaluate risk of dementia in patients with type 2 diabetes

AbstractBackgroundGlucagon‐like peptide 1 receptor agonists (GLP‐1 RA) have previously shown improved measures of memory and reduced phospho‐tau burden in preclinical animal models relevant to progressive cognitive impairment (Hansen. J Alzheimers Dis.2015;46:877‐88; Hansen. Brain Res.2016;1634:158‐70). Liraglutide and semaglutide are structurally similar GLP‐1 RAs associated with potent glucose‐lowering effect, body weight loss and cardiovascular benefits shown in large cardiovascular outcomes trials (CVOTs) (Marso. N Engl J Med.2016;375:311‐22; Marso. N Engl J Med.2016;375:1834‐44; Husain. N Engl J Med.2019;381:841‐51). In order to investigate the potential effects of GLP‐1 RA on dementia in a clinical setting, a post‐hoc analysis was conducted based on pooled data from three CVOTs.MethodLEADER, SUSTAIN 6 and PIONEER 6 were randomised, double‐blind, multicentre, placebo‐controlled CVOTs evaluating the cardiovascular effect of liraglutide or semaglutide vs. placebo, added to standard of care. The trials included patients with type 2 diabetes and established or high risk of cardiovascular disease. A post‐hoc analysis on pooled data from the three CVOTs was considered appropriate due to the similarities in trial design, patient population and treatment effects. Across all trials 15,820 patients with median follow‐up of 3.6 years were included in this analysis. Dementia‐related adverse events (AEs) were identified using Standardised MedDRA (version 21.1) Query for “dementia” narrow search terms. AE data collection across the trials differed in line with the regulatory requirements at the time of trial conduct. In LEADER and PIONEER 6 only serious AEs were systematically collected, while all AEs were collected in SUSTAIN 6. A time‐to‐event analysis based on the Cox proportional‐hazards model using treatment as covariate was used to estimate the hazard ratio for developing dementia.ResultAcross the three CVOTs, 15 GLP‐1 RA‐treated patients and 32 placebo‐treated patients were identified with development of dementia (Figure). Post‐hoc analysis on the pooled data showed a significant estimated hazard ratio of 0.47 [0.25; 0.86]95%CI in favour of the GLP‐1 RA treatment versus placebo.Conclusion Post‐hoc analysis based on pooled data from three double‐blinded CVOTs suggests, albeit with a low number of events, a reduced risk of dementia with liraglutide or semaglutide treatment in patients with type 2 diabetes.

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium-glucose cotransporter inhibitors with insulin for treatment of type 1 diabetes (Updated October 2020).

Dapagliflozin (SGLT-2 inhibitor) and sotagliflozin (SGLT1/2 inhibitor) are two of the drugs of SGLT inhibitor class which have been recommended by the National Institute for Health and Care Excellence (NICE) in people with type 1 diabetes with BMI ≥27kg/m2 . Dapagliflozin is licensed in the UK for use in the NHS while sotagliflozin may be available in future. These and possibly other SGLT inhibitors may be increasingly used in people with type 1 diabetes as new licences are obtained. These drugs have the potential to improve glycaemic control in people with type 1 diabetes with the added benefit of weight loss, better control of blood pressure and more time in optimal glucose range. However, SGLT inhibitors are associated with a higher incidence of diabetic ketoacidosis without significant hyperglycaemia. The present ABCD/Diabetes UK joint updated position statement is to guide people with type 1 diabetes and clinicians using these drugs help mitigate this risk and other potential complications. Particularly, caution needs to be exercised in people who are at risk of diabetic ketoacidosis due to low calorie diets, illnesses, injuries, starvation, excessive exercise, excessive alcohol consumption and reduced insulin administration among other precipitating factors for diabetic ketoacidosis.

Efectos del ejercicio en cirugía bariátrica

Introducción: El objetivo de esta revisión es analizar la literatura científica más actual acerca de los efectos del ejercicio en pacientes obesos o sometidos a cirugía bariátrica.
 Desarrollo: Se ha llevado a cabo una revisión de la literatura científica actual mediante una búsqueda sistematizada en PubMed, Scopus, Cinhal, Web Of Science y SPORTDiscus con los descriptores “bariatric surgery”, “exercise therapy” y “therapeutic exercise”, obteniendo finalmente 13 artículos.
 Se observó que el ejercicio produce beneficios en cuanto a composición corporal como pérdida de peso, aumento de masa magra, masa muscular e insulina en sangre y favorece la actividad fibrinolítica. Además, produce un aumento de la capacidad aeróbica y, por tanto, una mejora de la condición física.
 Conclusiones: Podemos concluir que el ejercicio es una herramienta efectiva en el tratamiento de pacientes con obesidad tanto antes como después de la cirugía.

Effect of the glucagon-like peptide-1 analogue liraglutide versus placebo treatment on circulating proglucagon-derived peptides that mediate improvements in body weight, insulin secretion and action: A randomized controlled trial.

To examine how circulating glucagon-like peptide-1 (GLP-1) concentrations during liraglutide treatment relate to its therapeutic actions on glucose and weight, and to study the effects of liraglutide on other proglucagon-derived peptides (PGDPs), including endogenous GLP-1, glucagon-like peptide-2, glucagon, oxyntomodulin, glicentin and major proglucagon fragment, which also regulate metabolic and weight control. Adults who were overweight/obese (body mass index 27-40 kg/m2 ) with prediabetes were randomized to liraglutide (1.8 mg/day) versus placebo for 14 weeks. We used specific assays to measure exogenous (liraglutide, GLP-1 agonist [GLP-1A]) and endogenous (GLP-1E) GLP-1, alongside five other PGDP concentrations during a mixed meal tolerance test (MMTT) completed at baseline and at week 14 (liraglutide, n = 16; placebo, n = 19). Glucose during MMTT, steady-state plasma glucose (SSPG) concentration for insulin resistance and insulin secretion rate (ISR) were previously measured. MMTT area-under-the-curve (AUC) was calculated for ISR, glucose and levels of PGDPs. Participants on liraglutide versus placebo had significantly (P ≤ .004) decreased weight (mean -3.6%, 95% CI [-5.2% to -2.1%]), SSPG (-32% [-43% to -22%]) and glucose AUC (-7.0% [-11.5% to -2.5%]) and increased ISR AUC (30% [16% to 44%]). GLP-1A AUC at study end was significantly (P ≤ .04) linearly associated with % decrease in weight (r = -0.54) and SSPG (r = -0.59) and increase in ISR AUC (r = 0.51) in the liraglutide group. Treatment with liraglutide significantly (P ≤ .005) increased exogenous GLP-1A AUC (median 310 vs. 262 pg/mL × 8 hours at baseline but decreased endogenous GLP-1E AUC [13.1 vs. 24.2 pmol/L × 8 hours at baseline]), as well as the five other PGDPs. Decreases in the PGDPs processed in the intestines are independent of weight loss, indicating a probable direct effect of GLP-1 receptor agonists to decrease their endogenous production in contrast to weight loss-dependent changes in glucagon and major proglucagon fragment that are processed in pancreatic alpha cells. Circulating GLP-1A concentrations, reflecting liraglutide levels, predict improvement in weight, insulin action and secretion in a linear manner. Importantly, liraglutide also downregulates other PGDPs, normalization of the levels of which may provide additional metabolic and weight loss benefits in the future.

Lifestyle modification for the management of atrial fibrillation.

Trials showing the benefit of weight loss (in combination with other strategies for managing risk factors) in atrial fibrillation have primarily used high-protein, low-glycemic-index diets, along with low-intensity exercise, to achieve reductions in body mass index (BMI).[1][1],[2][2] Patients with

The role of nutritional additives in prevention: dietary supplementation with Spirulina reduces myocardial damage and improves cardiac function post-myocardial infarction in swine

Abstract Introduction The outcome of acute ST-elevation myocardial infarction depends, to a large extent, on the size of the infarct. Myocardial damage due to infarction involves several pathogenic mechanisms among which excessive generation of reactive oxygen species and an exacerbated inflammatory reaction play a critical role. Spirulina is a dietary supplement made from blue-green algae (Arthrospira platensis) used to manage weight loss and metabolic syndrome disorders. In addition, Spirulina has experimentally shown to exert anti-oxidant and anti-inflammatory properties because its composition rich in antioxidants, polyunsaturated fatty acids, essential amino-acids, and minerals. Purpose The purpose of the present study was to investigate whether dietary supplementation with Spirulina may serve as a cardioprotective agent by attenuating cardiac damage and ventricular dysfunction due to myocardial infarction in a highly translatable animal model. Methods Pigs (n=10) were fed a normocholesterolemic diet supplemented with Spirulina (1 gr/animal/bid; n=5) or placebo (n=5) for 10 days and then they were subjected to myocardial infarction by means of 1.5h balloon occlusion of the mid left anterior descending coronary artery. Thereafter animals were reperfused for 2.5h and then sacrificed. Infarct size was assessed by TTC staining and ischemic and non-ischemic myocardial tissue was obtained for molecular analysis of cardioprotective kinases, anti-apoptotic- and anti-inflammatory- related markers. Biochemical analyses (lipid levels, kidney and liver parameters) and weight gain were monitored throughout the study. Results Supplementation with Spirulina led to an absolute significant reduction in infarct size of 10±1% of the left ventricle (LV) as compared to control animals (p<0.05). At a functional level, all animals displayed comparable LV ejection fraction (LVEF) prior-MI induction (control: 64.5±2.6%; Spirulina: 61.5±2.6%). However, after 2.5h of reperfusion control animals showed a worsening of 18.2±2.0% LVEF whereas it was only of 7.2±2.5% in Spirulina-administered pigs (60% relative improvement vs. controls; p<0.05). At a molecular level, Spirulina administered animals showed higher expression of PI3K, Bcl-2, and Cox-2 and reduced content of MCP-1 in the jeopardized myocardium. Supplementation with Spirulina for 10 days markedly reduced total- cholesterol by 25% (p<0.04), LDL- cholesterol by 47% (p<0.05), enhanced HDL-cholesterol concentration by 79% (p<0.03) and limited weight gain (p<0.05) as compared to controls. Kidney and liver enzymes were found to be within the physiological range. Conclusion Supplementation with Spirulina, beyond its proven benefits in weight loss and lipid profile, exerts cardioprotection by inducing myocardial survival kinases, and triggering cytoprotective and anti-inflammatory mechanisms, thereby limiting cardiac damage and improving ventricular contractility post-MI. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministerio de Ciencia Innovacion y Universidades / Instituto de Salud Carlos III

Does the weight loss efficacy of alternate day fasting differ according to sex and menopausal status?

Background and aimsThis study examined if the weight loss and metabolic benefits of alternate day fasting (ADF) varies according to sex and menopausal status in adults with obesity. Methods and resultsThis secondary analysis pooled the data of men and women (n = 75) who participated in three 12-week ADF studies (500 kcal fast day; alternated with an ad libitum intake feast day). Body weight decreased in premenopausal women (−4.6 ± 3.2%), postmenopausal women (−6.5 ± 3.2%) and men (−6.2 ± 4.4%) (main effect of time, P < 0.001), with no difference between groups (no group × time interaction). Energy intake on fast days was higher than prescribed in all groups (∼400–500 excess kcal consumed), with no differences between groups. Fat mass, lean mass, fasting insulin, and insulin resistance, and blood pressure decreased similarly in all groups (main effect of time, P < 0.05 for all comparisons). LDL cholesterol decreased more in postmenopausal versus premenopausal women (group × time interaction, P = 0.01). Fasting glucose, HDL cholesterol, and triglycerides remained unchanged in all groups. ConclusionThese findings suggest that the weight loss and metabolic benefits of ADF do not generally vary according to sex or menopausal status in adults with obesity. Trial registrationClinicaltrials.gov, NCT00960505; NCT03528317.

Pharmacokinetics and Clinical Implications of Oral Semaglutide for Type 2 Diabetes Mellitus.

Since the approval of subcutaneous glucagon-like peptide-1 receptor agonists, this therapeutic class has become a preferred choice for the management of type 2 diabetes due to A1C reduction, minimal risk of hypoglycemia, weight loss, and cardiovascular benefit. An oral option, with gastrointestinal absorption, would overcome any potential fear of injection among patients. Oral semaglutide has been studied in randomized controlled trials within the PIONEER program. From a robust pool of literature with a global patient population, oral semaglutide has been an effective option as monotherapy and combination therapy to improve clinical outcomes, such as A1C and body weight from baseline to week 78, depending on the randomized controlled trial. In addition, a noninferiority result was observed with oral semaglutide versus placebo in a cardiovascular outcomes trial in patients with type 2 diabetes with established cardiovascular disease or risk factors. Similar to injectable glucagon-like peptide 1 receptor agonists, transient nausea and vomiting was seen with oral semaglutide. Overall, this new oral option may be a choice for patients with barriers to injectable therapy. This review evaluates and summarizes the pharmacokinetics, pharmacodynamics, and clinical application of oral semaglutide in patients with type 2 diabetes.

The Impact of Bariatric Surgery Compared to Medical Therapy on Health-Related Quality of Life in Subjects with Obesity and Type 2 Diabetes Mellitus.

The adverse implications of obesity extend beyond physical health to include negative impact on quality of life (QoL), mood, and eating habits. While bariatric surgery provides successful weight loss and metabolic benefits, studies describe conflicting results on QoL and mood-related outcomes. Patients (n = 140) with class II/III obesity and T2DM were recruited from 2015 to 2019, and stratified based on medical or surgical treatment. Questionnaires including the Hospital Anxiety and Depression Scale, Euro QoL visual analogue scale (EQ-VAS), and Revised 21-item Three-Factor Eating Questionnaire (TFEQ-R21) were recorded at baseline, 6months, and 12months after treatment. At baseline, the surgical group (n = 55) and medical group (n = 85) had no significant difference in questionnaire outcomes. At 6 and 12months, EQ-VAS was higher in the surgical group (12months surgical 82.00 ± 12.64, medical 72.81 ± 16.56, p = 0.001), with greater improvement from baseline. HADS-D scores at 12months were lower in the surgical group (surgical 2.60 ± 2.88, medical 3.90 ± 3.58, p = 0.025). At 12months, the surgical group also had better TFEQ-R21 scores, with higher cognitive restraint scores (surgical 19.09 ± 3.00, medical 16.69 ± 3.61, p < 0.001), and lower scores for uncontrolled eating (surgical 14.96 ± 3.87, medical 17.89 ± 5.34, p = 0.001). In the treatment of patients with obesity and T2DM, bariatric surgery resulted in improved QoL outcomes at 12months compared to medical therapy. This could be related to improvement in weight and metabolic outcomes, and altered gut-brain axis communication. This is the first prospective study assessing the impact of bariatric surgery on health-related QoL in Asia compared against a control group who received medical therapy.

Short-term multiorgan metabolic benefits of rapid weight loss after sleeve gastrectomy in severely obese patients

Background Sleeve gastrectomy (SG) has become the most prevalent bariatric-metabolic surgical approach in the United States. Its popularity among surgeons and patients is mainly due to a better safety profile and less overall morbidity, with broad benefits from a systemic and metabolic perspective. Objective Comprehensively describe the short-term multiorgan metabolic effects of rapid weight loss after SG. Setting Academic hospital, United States. Methods We retrospectively reviewed the charts of patients that underwent SG at our institution between 2012 and 2016. We analyzed the required variables to calculate multiple risk scores, such as cardiovascular, hypertension, and diabetes risk scores. Furthermore, the renal and hepatic functions and the metabolic and hematologic profiles were assessed at 12 months of follow-up. Results A total of 1002 patients were included in the analysis. The percentage of excess body mass index loss was, on average, 65% at 12 months of follow-up. We observed a positive cardio-renal-hepatic improvement, demonstrated by a substantial reduction of the 10-year cardiovascular risk. We noticed an improvement of renal function, which was more significant in chronic kidney disease (stage ≥2), and a significant improvement on liver function tests (measured by decreased aspartate aminotransferase and alanine transaminase) at 12 months of follow-up. Our data also show a positive impact on decreasing the risk of developing hypertension and type 2 diabetes. There was a positive impact on the lipid profile, with the exception of low-density lipoprotein. Conclusion There are significant short-term benefits on multiorgan metabolic parameters after rapid weight loss in severely obese patients undergoing sleeve gastrectomy.

Comparing the Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists with Sodium-Glucose Cotransporter 2 Inhibitors for Obese Type 2 Diabetes Patients Uncontrolled on Metformin: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Introduction To conduct the first meta-analysis of randomized controlled trials (RCTs) comparing glucagon-like peptide 1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) for obese type 2 diabetes (T2D) patients uncontrolled on metformin. Methods We searched Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid, and Web of Science from inception to May 14, 2020, without language restrictions for eligible RCTs. The primary outcome is the mean change from baseline in glycated haemoglobin (HbA1c). Results Totally, 3 RCTs enrolled 2066 patients were identified. Compared with SGLT-2is, treatment with GLP-1RAs achieved significant reduced HbA1c by 0.40% (95% CI: −0.54, −0.25; p < 0.00001), fasting blood glucose (FBG) by 0.17 mmol/L (95% CI: −0.31, −0.04; p=0.01), and postprandial blood glucose (PBG) by 0.32 mmol/L (95% CI: −0.49, −0.14; p=0.0003) for obese T2D patients uncontrolled on metformin. The significant benefit of weight loss was seen in semaglutide (MD: −0.75; 95% CI: −1.18, −0.31; p < 0.0007). No significant difference was detected between GLP-1RAs and SGLT-2is in overall adverse events (RR: 1.03; 95% CI: 0.98, 1.09; p=0.76), but gastrointestinal events showed higher occurrence in GLP-1RAs groups compared with SGLT-2is (RR: 1.62; 95% CI: 1.37, 1.93; p < 0.00001). Subgroup analyses revealed that follow-up time did not statistically influence glycemic control. Conclusion GLP-1RAs are superior to SGLT-2is for obese T2D patients uncontrolled on metformin in glycemic control without an increase in adverse events except for a higher occurrence in gastrointestinal events. Future large longer-term follow-up clinical trials are needed to provide more evidence about the sustainable effects and safety of GLP-1RAs compared with SGLT-2is.

Weight maintenance interventions for people with type 2 diabetes mellitus: a systematic review protocol

BackgroundWeight loss maintenance is a challenge for people with type 2 diabetes mellitus (T2DM), which attenuates the long-term benefits of weight loss for diabetes management. Medication, specific dietary requirements and the psychosocial burden of T2DM signify that weight loss maintenance designed for obesity may not suit people with T2DM. The primary objective of this review is to comprehensively evaluate existing weight maintenance interventions for people with or at high risk of T2DM.MethodsWe registered a protocol for the systematic review and meta-analysis of randomised and non-randomised weight maintenance interventions for T2DM. Studies included will have been carried out in adults with clinical diagnosis of T2DM or pre-diabetes. All intervention types will be accepted (e.g. behavioural/lifestyle change and pharmacological). The primary outcomes will be weight control, glycaemic control and adverse effects. Secondary outcomes will include cardiovascular risk factors (e.g. total cholesterol, LDL-cholesterol, blood pressure control), psychological wellbeing (including health-related quality of life), change in glucose medication and waist circumference. Multiple electronic databases will be searched such as MEDLINE, EMBASE, Web of Science, PsychINFO and international registers (e.g. Cochrane Central Register of Controlled Trials, WHO ICTRP). OpenGrey will be searched for grey literature. Two researchers will screen all citations and abstracts. This process will also be conducted by an additional researcher using a semi-automated tool to reduce human error. Full-text articles will be further examined by the researchers to select a final set for further analysis, and a narrative synthesis of the evidence will be presented. Potential sources of heterogeneity will be assessed, and a meta-analysis will be conducted if feasible. Risk of bias will be evaluated using the Cochrane risk of bias tool and the certainty of evidence using the GRADE (grading of recommendations, assessment, development and evaluation) approach.DiscussionThis review will critically appraise existing weight maintenance interventions targeting T2DM. Findings will inform future intervention development to support people with T2DM delay weight regain and prolong successful diabetes management.Systematic review registrationPROSPERO CRD42020168032

Intervention Enhancement Strategies Among Adults With Type 2 Diabetes in a Very Low–Carbohydrate Web-Based Program: Evaluating the Impact With a Randomized Trial

BackgroundAdults with type 2 diabetes may experience health benefits, including glycemic control and weight loss, from following a very low–carbohydrate, ketogenic (VLC) diet. However, it is unclear which ancillary strategies may enhance these effects.ObjectiveThis pilot study aims to estimate the effect sizes of 3 intervention enhancement strategies (text messages, gifts, and breath vs urine ketone self-monitoring) that may improve outcomes of a 12-month web-based ad libitum VLC diet and lifestyle intervention for adults with type 2 diabetes. The primary intervention also included other components to improve adherence and well-being, including positive affect and mindfulness as well as coaching.MethodsOverweight or obese adults (n=44; BMI 25-45 kg/m2) with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.5%), who had been prescribed either no glucose-lowering medications or metformin alone, participated in a 12-month web-based intervention. Using a 2×2×2 randomized factorial design, we compared 3 enhancement strategies: (1) near-daily text messages about the intervention’s recommended behaviors (texts n=22 vs no texts n=22), (2) mailed gifts of diet-relevant foods and cookbooks (6 rounds of mailed gifts n=21 vs no gifts n=23), and (3) urine- or breath-based ketone self-monitoring (urine n=21 vs breath n=23). We assessed HbA1c and weight at baseline and at 4, 8, and 12 months. We evaluated whether each strategy exerted a differential impact on HbA1c and weight at 12 months against an a priori threshold of Cohen d of 0.5 or greater.ResultsWe retained 73% (32/44) of the participants at 12 months. The intervention, across all conditions, led to improvements in glucose control and reductions in body weight at the 12-month follow-up. In intent-to-treat (ITT) analyses, the mean HbA1c reduction was 1.0% (SD 1.6) and the mean weight reduction was 5.3% (SD 6.0), whereas among study completers, these reductions were 1.2% (SD 1.7) and 6.3% (SD 6.4), respectively, all with a P value of less than .001. In ITT analyses, no enhancement strategy met the effect size threshold. Considering only study completers, 2 strategies showed a differential effect size of at least a d value of 0.5 or greaterConclusionsText messages, gifts of food and cookbooks, and urine-based ketone self-monitoring may potentially enhance the glycemic or weight loss benefits of a web-based VLC diet and lifestyle intervention for individuals with type 2 diabetes. Future research could investigate other enhancement strategies to help create even more effective solutions for the treatment of type 2 diabetes.Trial RegistrationClinicalTrials.gov NCT02676648; http://clinicaltrials.gov/ct2/show/NCT02676648

Impact of Weight Change in Adults with Type 2 Diabetes Mellitus: A Literature Review and Critical Analysis.

ObjectiveWeight reduction is a key component of diabetes management in adults with type 2 diabetes mellitus (T2DM), yet the benefits of weight loss in T2DM patients have been difficult to quantify. We examined the medical literature regarding the relationships between weight change and 1) glycemic control and 2) cost and resource use.MethodsSystematic searches were conducted in the electronic databases Embase, MEDLINE, and the Cochrane Database of Systematic Reviews to identify publications regarding the impact of weight change on T2DM outcomes from 2007 onward. Identified publications were screened for relevance against predefined eligibility criteria, and methodological approaches and results were extracted. Evidence for the impact of weight change on outcomes was evaluated and used to identify strengths, limitations, and gaps in the current literature.ResultsThe number of studies meeting eligibility criteria for each outcome was: glycemic control (n=38) and cost and resource use (n=11). The relationship between weight change and glycemic control was dependent on the interplay of multiple factors, eg, the weight loss interventions employed, the antidiabetic medication classes used, the time horizon, and baseline BMI and glycemic control. With respect to cost and resource use, the review indicated that savings were associated with weight loss, and increased costs were associated with weight gain.ConclusionStudies regarding weight change in T2DM patients demonstrated varying effects on glycemic control and a positive association with costs and resource use, where weight loss was associated with decreased costs and resource use. Future studies may be able to clarify these relationships.

Investigating lay beliefs regarding the effect of weight loss on health

Objective Individuals with obesity are often recommended weight loss for their health; however, the amount of weight loss that is recommended varies. Lay people’s beliefs about weight loss could influence the types of behaviours they view as necessary for people with obesity. The present study explored lay beliefs regarding the health benefits of varying degrees of weight loss. Design Participants (379 community members and 235 students) read information about an obese target who lost varying amounts of weight (none vs. modest vs. substantial) following behaviour changes. Main outcome Participants evaluated the target’s health and recommended health-related behaviours to the target. Results The substantial weight-loss target, but not the modest weight-loss target, was perceived as being healthier than the no weight-loss target. There were no differences in behaviour recommendations made to the no weight-loss and modest weight-loss targets, with most participants recommending further weight loss to both targets. Conclusions Lay people appear to view substantial, but not modest, weight loss as beneficial to health, and they recommend further, more unrealistic amounts of weight loss to obese individuals who have already achieved modest weight loss. A failure to recognise the health benefits of modest weight loss may contribute to unrealistic weight loss goals.