Proven Fat Loss Adjuvants

[STENDEC 7,108]

Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16.
Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial.
O'Neil PM1, Birkenfeld AL2, McGowan B3, Mosenzon O4, Pedersen SD5, Wharton S6, Carson CG7, Jepsen CH7, Kabisch M7, Wilding JPH8.
Obesity and Endocrinology Research, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. Electronic address: j.p.h.wilding@liverpool.ac.uk.

 

Abstract

 

BACKGROUND:
Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss.

 

METHODS:
We did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m2 or more. We randomly assigned participants (6:1) to each active treatment group (ie, semaglutide [0·05 mg, 0·1 mg, 0·2 mg, 0·3 mg, or 0·4 mg; initiated at 0·05 mg per day and incrementally escalated every 4 weeks] or liraglutide [3·0 mg; initiated at 0·6 mg per day and escalated by 0·6 mg per week]) or matching placebo group (equal injection volume and escalation schedule to active treatment group) using a block size of 56. All treatment doses were delivered once-daily via subcutaneous injections. Participants and investigators were masked to the assigned study treatment but not the target dose. The primary endpoint was percentage weight loss at week 52. The primary analysis was done using intention-to-treat ANCOVA estimation with missing data derived from the placebo pool. This study is registered with ClinicalTrials.gov, number NCT02453711.

 

FINDINGS:
Between Oct 1, 2015, and Feb 11, 2016, 957 individuals were randomly assigned (102-103 participants per active treatment group and 136 in the pooled placebo group). Mean baseline characteristics included age 47 years, bodyweight 111·5 kg, and BMI 39·3 kg/m2. Bodyweight data were available for 891 (93%) of 957 participants at week 52. Estimated mean weight loss was -2·3% for the placebo group versus -6·0% (0·05 mg), -8·6% (0·1 mg), -11·6% (0·2 mg), -11·2% (0·3 mg), and -13·8% (0·4 mg) for the semaglutide groups. All semaglutide groups versus placebo were significant (unadjusted p≤0·0010), and remained significant after adjustment for multiple testing (p≤0·0055). Mean bodyweight reductions for 0·2 mg or more of semaglutide versus liraglutide were all significant (-13·8% to -11·2% vs -7·8%). Estimated weight loss of 10% or more occurred in 10% of participants receiving placebo compared with 37-65% receiving 0·1 mg or more of semaglutide (p<0·0001 vs placebo). All semaglutide doses were generally well tolerated, with no new safety concerns. The most common adverse events were dose-related gastrointestinal symptoms, primarily nausea, as seen previously with GLP-1 receptor agonists.

 

INTERPRETATION:
In combination with dietary and physical activity counselling, semaglutide was well tolerated over 52 weeks and showed clinically relevant weight loss compared with placebo at all doses.

 

PMID: 30122305 

 

 

Weight loss of +10% in a year is hella impressive. This stuff is also now available as an oral formulation.

[KCASANJO594 7,340]

I bet you'd have to find a really edgy doc that you rx this for weight loss, though. 

 

I have an upcoming physical, so I might try to walk my guy down this path. 

[Something Anonymous 699]

My wife takes Teduglutide which is a GLP-2 peptide. I wonder if it has similar effects. 

[KCASANJO594 7,340]

22 minutes ago, Something Anonymous said:

My wife takes Teduglutide which is a GLP-2 peptide. I wonder if it has similar effects. 

 

90 seconds of searching turns it up as an adjuvant to short-bowel syndrome that reverses weight loss from the SBS.

 

I'm guessing 'no'.

[Something Anonymous 699]

2 hours ago, Emperor G_D said:

 

90 seconds of searching turns it up as an adjuvant to short-bowel syndrome that reverses weight loss from the SBS.

 

I'm guessing 'no'.

 

Yes, but you have to understand that short bowel causes malnourishment by rapid transit and malabsorption. Increasing the surface area and slowing transit will increase the amount of calories absorbed in an SBS patient irrespective of anorectic or thermogenic properties.

 

One of the most common listed side effects of Teduglutide is “change in appetite”. An SBS patient could have a reduced appetite and still gain weight through enhanced absorption. For perspective my wife went from 5’7” and 90lbs to 100lbs over the past 6 months of use but she eats sparingly and gets nausea post-injection. 

[STENDEC 7,108]

J Manag Care Spec Pharm. 2018 Sep;24(9-a Suppl):S14-S29. doi: 10.18553/jmcp.2018.24.9-a.s14.
Glycemic Efficacy, Weight Effects, and Safety of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists.
Handelsman Y1, Wyne K2, Cannon A3, Shannon M4, Schneider D5.

Abstract
This article provides an overview of the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic GLP-1 receptors, which increases insulin secretion, delays gastric emptying, and increases satiety. As a class, GLP-1 RAs lower A1c levels and have been associated with reductions in weight and blood pressure and reduced fluctuations in glucose levels, and they have a low risk of hypoglycemia. Exenatide extended release (ER) and dulaglutide monotherapy have shown similar or superior reductions in A1c and weight compared with various oral antidiabetic drugs (OADs). Semaglutide has been shown to reduce both A1c and body weight compared with placebo and, in head-to-head studies versus both exenatide ER and dulaglutide, showed greater reductions in A1c and body weight. Once-weekly GLP-1 RAs have also been evaluated as add-on therapy in the continuum of care for the treatment of T2DM in combination with a variety of background medications, including 1 or more OADs (metformin, sulfonylureas, and/or thiazolidinediones), basal insulin, and prandial insulin. Gastrointestinal adverse events (e.g., nausea, vomiting, and diarrhea) are the most common side effects with once-weekly GLP-1 RAs. Rates of hypoglycemia, and especially major/severe hypoglycemia, are low with once-weekly GLP-1 RAs but, as expected, are higher when used in combination with sulfonylureas or insulin. These once-weekly GLP-1 RAs provide a safe and effective treatment option for patients with T2DM and may offer improved convenience and possibly greater adherence compared with daily GLP-1 RAs.

 

 

PMID: 30156445 

 

FFT

[STENDEC 7,108]

4 hours ago, Emperor G_D said:

I have an upcoming physical, so I might try to walk my guy down this path.

 

Related drug, liraglutide is indicated for obesity, specifically coincident with HTN.

[KCASANJO594 7,340]

1 hour ago, STENDEC said:

 

Related drug, liraglutide is indicated for obesity, specifically coincident with HTN.

 

Looks like Victoza might be covered for me. Good timing.

[STENDEC 7,108]

Almost a 10% change in BF percentage after 24 weeks is not bad.

 

 

A Randomized Controlled Trial of Long-Term (R)-α-Lipoic Acid Supplementation Promotes Weight Loss in Overweight or Obese Adults without Altering Baseline Elevated Plasma Triglyceride Concentrations
Gerd Bobe, Alexander J Michels, Wei-Jian Zhang, Jonathan Q Purnell, Clive Woffendin, Cliff Pereira, Joseph A Vita, Nicholas O Thomas, Maret G Traber, Balz Frei ... Show more
The Journal of Nutrition, 21 July 2020 

α-Lipoic acid (LA) is a dietary supplement for maintaining energy balance, but well-controlled clinical trials in otherwise healthy, overweight adults using LA supplementation are lacking.

The primary objective was to evaluate whether LA supplementation decreases elevated plasma triglycerides in overweight or obese adults. Secondary aims examined if LA promotes weight loss and improves oxidative stress and inflammation.

Overweight adults [n = 81; 57% women; 21–60 y old; BMI (in kg/m2) ≥ 25] with elevated plasma triglycerides ≥100 mg/dL were enrolled in a 24-wk, randomized, double-blind, controlled trial, assigned to either (R)-α-lipoic acid (R-LA; 600 mg/d) or matching placebo, and advised not to change their diet or physical activity. Linear models were used to evaluate treatment effects from baseline for primary and secondary endpoints.

R-LA did not decrease triglyceride concentrations, but individuals on R-LA had a greater reduction in BMI at 24 wk than the placebo group (−0.8; P = 0.04). The effect of R-LA on BMI was correlated to changes in plasma triglycerides (r = +0.50, P = 0.004). Improvement in body weight was greater at 24 wk in R-LA subgroups than in placebo subgroups. Women and obese participants (BMI ≥ 35) showed greater weight loss (−5.0% and −4.8%, respectively; both P < 0.001) and loss of body fat (−9.4% and −8.6%, respectively; both P < 0.005). Antioxidant gene expression in mononuclear cells at 24 wk was greater in the R-LA group (Heme oxygenase 1 [HMOX1] : +22%; P = 0.02) than in placebo. Less urinary F2-isoprostanes (−25%; P = 0.005), blood leukocytes (−10.1%; P = 0.01), blood thrombocytes (−5.1%; P = 0.03), and ICAM-1 (−7.4%; P = 0.04) at 24 wk were also observed in the R-LA group than in placebo.

Long-term LA supplementation results in BMI loss, greater antioxidant enzyme synthesis, and less potential for inflammation in overweight adults. Improved cellular bioenergetics is also evident in some individuals given R-LA.

[STENDEC 7,108]

Confirms mild weight/fat loss found in earlier studies.

 

 

Journal of Clinical Nutrition 2018 Apr;37(2):419-428. doi: 10.1016/j.clnu.2017.06.002. Epub 2017 Jun 8.
Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials
Nazli Namazi 1, Bagher Larijani 2, Leila Azadbakht 3

Previous studies have supported positive roles of antioxidant supplements on weight-loss. One antioxidant supplement is Alpha-lipoic acid. However, recommending ALA as an anti-obesity supplement remains controversial. Accordingly, the purpose of the present study was to perform a meta-analysis on the effects of ALA supplement on anthropometric indices among adult subjects.

 

We searched five electronic databases till September 2016. Placebo-controlled clinical trials were included. Weighted Mean Difference (WMD) was pooled using a random-effects model.

 

Findings of 12 included trials indicated that ALA supplement reduced body weight (WMD: -0.69 kg; 95% CI: -1.27, -0.10; I2 = 0%) and BMI (WMD: -0.38 kg/m2; 95% CI: -0.53, -0.24; I2 = 0%) significantly compared to the placebo group. However, its effects on Waist Circumference (WC) was not significant (WMD: -0.30 cm; 95% CI: -1.18, 0.58; I2 = 17.8%). Stratification by health status indicated that ALA decreased WC in unhealthy subjects (WMD: -2.00 cm; 95% CI: -4.19, 0.19; I2 = 1.3%) more than healthy individuals (0.03 cm; 95% CI: -0.69, 0.75; I2 = 0%).

Conclusions: The present study revealed that supplementation with ALA slightly but significantly decreased body weight and BMI. Safe dosage for ALA is up to 1200 mg/day. However, it seems that ALA cannot be cost-effective. Further studies are needed to clarify the effects of ALA on metabolic parameter in unhealthy obese individuals.

 

PMID: 28629898

[KCASANJO594 7,340]

I've been taking ALA since the article that you read was published.

 

Good old suppversity!

[STENDEC 7,108]

Have you ever played around with berberine?

 

 

[KCASANJO594 7,340]

14 minutes ago, STENDEC said:

Have you ever played around with berberine?

 

 

 

I took it for a fair long while. I stopped taking it because of the gastro sides. It's like metformin on me. 

[STENDEC 7,108]

1 hour ago, Emperor G_D said:

It's like metformin on me. 

 

Seems very similar to metformin in many respects.

[STENDEC 7,108]

Biomed Pharmacother 2020 Jul;127:110137. doi: 10.1016/j.biopha.2020.110137. Epub 2020 Apr 27.
The effect of Berberine on weight loss in order to prevent obesity: A systematic review
Zahra Ilyas 1, Simone Perna 1, Salwa Al-Thawadi 1, Tariq A Alalwan 1, Antonella Riva 2, Giovanna Petrangolini 2, Clara Gasparri 3, Vittoria Infantino 4, Gabriella Peroni 5, Mariangela Rondanelli 6

This study provides a critical overview of experimental studies in vitro, in humans, and in animals that evaluated the efficacy of Berberine and its effect on management of obesity and the related metabolic consequences. As a result of this review, we summarized the effects of Berberine in different models and the related mechanism of actions. In preclinical models, Berberine demonstrates that it affects gut microbiota by reducing diversity of microbes starting at a dosage of 100 mg/kg/day. Moreover, in animal models, Berberine explicates an action on glucose through the inhibition of α-glycosidase at a dose of 200 mh/kg/day. Berberine is also known to be effective against differentiation of adipocytes through a decrease in LXRs, PPARs, and SREBPs expression at 150 mg/kg/day. Other mechanism ascribed to Berberine are related to its inhibition of hepatic gluconeogenesis through the Phospheoenolpyruvate carboxykinase (PEPCK), Glucose-6-phosphate (G6Pase) and AMP-activated protein kinase (AMPK). Furthermore, Berberine (associated to Red Yeast Rice) is effective in decreasing lipid levels in rats, which consequently lowers the change of weight gain at dosage of 40 mg/kg to 380 mg/kg/day. All the above preclinical data are confirmed in human studies where Berberine can modulate the diversity of gut microbes at the dose of 500 mg/day. In addition, Berberine is found to have a beneficial impact on gene regulation for the absorption of cholesterol at a daily dose of 300 mg in humans, an amelioration on glucose accumulation at 1.0 g daily dose was also observed. For all these reasons, this review gives an important good account of the impact of Berberine in obesity treatment and prevention.

 

PMID: 32353823

 

FFT

[KCASANJO594 7,340]

11 minutes ago, STENDEC said:

 

Seems very similar to metformin in many respects.

 

Yeah, that's why I drew the comparison. 

 

Might be interesting to add it in again now that I'm better, diet-wise. I think all of the things I tried for so many years were for naught, because you can only do so much when you're in a 1-2000 kcal surplus daily. 

[dr. frankenstein 493]

.

 

...no bad

 

Novo Nordisk’s semaglutide demonstrates superior weight loss versus placebo in STEP 4 trial

https://www.clinicaltrialsarena.com/comment/novo-nordisk-semaglutide-weight-loss/

 

"The study reports that following an initial 20-week period, the 803 people who reached the target dose of semaglutide 2.4mg had a reduced mean body weight from 107.2kg to 96.1kg."

 

"The primary endpoint of the trial was achieved by demonstrating that, of all randomised patients, those who continued with semaglutide 2.4mg for 48 weeks, following the initial 20-week period, achieved an additional mean weight loss of 7.9% from a mean body weight at randomisation of 96.1kg" 

 

-----

 

But

 

Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin

https://pubmed.ncbi.nlm.nih.gov/31530666/

Diabetes Care 2019 Dec; 42(12): 2272-2281.

 

 

"Superiority of body weight reduction at week 26 with oral semaglutide over empagliflozin was not confirmed (treatment policy estimand −3.8 vs. −3.7 kg; ETD −0.1 kg [95% CI −0.7, 0.5]; P = 0.7593)." 

 

 

Rybelsus vs Jardiance.

.

.

[STENDEC 7,108]

The effects of grape seed extract (Vitis vinifera) supplement on inflammatory markers, neuropeptide Y, anthropometric measures, and appetite in obese or overweight individuals: A randomized clinical trial
Maryam Parandoosh  Reyhaneh Yousefi  Hoda Khorsandi  Omid Nikpayam  Atoosa Saidpour  Hossein Babaei
First published: 11 November 2019 https://doi.org/10.1002/ptr.6529Citations: 4

Background
Grape seed extract (GSE) is a natural supplement known for its various health benefits, including anti‐inflammatory effect. This study aimed to evaluate the effects of GSE supplementation on inflammatory markers, neuropeptide Y, anthropometric measurements, and appetite in obese or overweight individuals.

 

Methods and materials
A randomized, double‐blind clinical trial was performed on 40 obese or overweight subjects who were randomly assigned to receive GSE (300 mg/day) or placebo for a period of 12‐weeks. Both groups were under a restricted calorie diet (RCD)(~250 kcal lower than the estimated energy requirement). Anthropometric measurements, biochemical biomarkers and dietary intakes were determined during the study period.

 

Results
The reductions of body weight, body mass index, waist circumference, and waist to hip ratio were significantly higher in the GSE group compared to the placebo group (P = 0.045, 0.033, 0.029, and 0.021, respectively). Lower levels of neuropeptide Y, tumor necrosis factor alpha, and high sensitivity C‐reactive protein were observed in the GSE group in comparison with the placebo group (P = 0.041, 0.001, and 0.034, respectively).

 

Conclusion
GSE supplement with a RCD has favorable effects in reducing anthropometric measurements and inflammatory markers in obese or overweight individuals, and may play an effective role in the treatment of obesity.

 

FFT

[KCASANJO594 7,340]

On 8/21/2020 at 12:14 PM, dr. frankenstein said:

.

 

...no bad

 

Novo Nordisk’s semaglutide demonstrates superior weight loss versus placebo in STEP 4 trial

https://www.clinicaltrialsarena.com/comment/novo-nordisk-semaglutide-weight-loss/

 

"The study reports that following an initial 20-week period, the 803 people who reached the target dose of semaglutide 2.4mg had a reduced mean body weight from 107.2kg to 96.1kg."

 

"The primary endpoint of the trial was achieved by demonstrating that, of all randomised patients, those who continued with semaglutide 2.4mg for 48 weeks, following the initial 20-week period, achieved an additional mean weight loss of 7.9% from a mean body weight at randomisation of 96.1kg" 

 

 

 

Nice study, but I doubt many could afford 2.4mg/wk, or that any insurances would cover it. Most anti-obesity treatments are of course stigmatized since fat people should just change their ways...

 

FTR, I am transitioning from Liraglutide to Semaglutide this month, so hopefully some more weight loss from that.

[STENDEC 7,108]

Really small study but impressive results.

 

This is the same drug that Novartis tried to use to treat a rare muscle-wasting disease a few years ago and failed.

 

Medication shows promise for weight loss in patients with obesity, diabetes
THE OBESITY SOCIETY

Research News

 
SILVER SPRING, Md.--A new study confirms that treatment with Bimagrumab, an antibody that blocks activin type II receptors and stimulates skeletal muscle growth, is safe and effective for treating excess adiposity and metabolic disturbances of adult patients with obesity and type 2 diabetes.

 

"These exciting results suggest that there may be a novel mechanism for achieving weight loss with a profound loss of body fat and an increase in lean mass, along with other metabolic benefits," said Steve Heymsfield, MD, FTOS, past president of The Obesity Society and corresponding author of the study. Heymsfield is professor and director of the Metabolism and Body Composition Laboratory at the Pennington Biomedical Research Center in Baton Rouge, La.

 

A total of 75 patients with type 2 diabetes, body mass index between 28 and 40 and glycated hemoglobin A1c levels between 6.5 percent and 10 percent were selected for the phase 2 randomized clinical trial. Patients were injected with either Bimagrumab or a placebo (a dextrose solution) every 4 weeks for 48 weeks. Both groups received diet and exercise counseling. The research took place at nine sites in the United States and the United Kingdom from February 2017 to May 2019.

 

At the end of the 48-week study, researchers found a nearly 21 percent decrease in body fat in the Bimagrumab group compared to 0.5 percent in the placebo group. The results also revealed the Bimagrumab group gained 3.6 percent of lean mass compared with a loss of 0.8 percent in the placebo group. The combined loss in total body fat and gain in lean mass led to a net 6.5 percent reduction in body weight in patients receiving Bimagrumab compared with 0.8 percent weight loss in their counterparts receiving the placebo.

 

The sample size of 75 participants was a limitation of the study. There was also a gender imbalance across the groups with more women randomized to Bimagrumab and more men to the placebo.

 

Partial results of this study were presented during a research forum titled "Emerging Pharmacological Anti-obesity Therapies" at ObesityWeek® 2019 in Las Vegas, Nev.

[KCASANJO594 7,340]

I WANT SOME BIMAGRUMAB

[KCASANJO594 7,340]

Sounds like a shitty study, though...

[STENDEC 7,108]

1 hour ago, KCASANJO594 said:

Sounds like a shitty study, though...

 

What makes you say that?

[KCASANJO594 7,340]

5 minutes ago, STENDEC said:

 

What makes you say that?

 

Aside from small size, the randomization across gender wasn't very good...

[STENDEC 7,108]

Have to wait for the actual study to be published to see if the gender issue was significant or not.