Obesity

Intensive weight loss eliminates type 2 diabetes

Intensive weight loss eliminates type 2 diabetes

Type 2 diabetes has traditionally been perceived as a non-reversible, progressive condition that eventually requires insulin therapy. Recent evidence, however, has been mounting in showing that type 2 diabetes, if diagnosed early, can be fully reversed with intense lifestyle modifications in a subset of patients.

In the current study published in Diabetic Medicine in September 2019, investigators followed prospectively about 900 adult diabetes patients age 40-70 over five years. Individuals who lost more than 10% of body weight within the first few years of the study, had the best chance of eliminating diabetes, as documented by A1c <6.5%.

At the study conclusion, 30% of adults achieved diabetes remission. Important to note that remission or reversal was accomplished independently of any specific lifestyle modifications, except the >10% weight loss.

More clinical trials are needed to confirm the above results. Nonetheless, intensive weight loss at the onset of diabetes diagnosis could be reasonable general advice for people who are overweight or obese.

GT

New FDA approval: semaglutide, the first oral GLP-1 agonist for type 2 diabetes

New FDA approval: semaglutide, the first oral GLP-1 agonist for type 2 diabetes

The FDA has now approved the first oral semaglutide, Rybelsus, for the treatment of type 2 diabetes. This approval marks a breakthrough advancement in the field of clinical diabetology. Rybelsus is the first "protein" based molecule to be administered orally and not subcutaneously via an injection.

Oral administration of semaglutide is made possible through the use of SNAC compound. SNAC helps escort and transport the semaglutide intact across the gastrointestinal epithelial cells. It assists in bypassing the harsh acidic environment of the stomach.

Various clinical trials, under the name PIONEER, have consistently shown A1c improvements and weight loss benefits with Rybelsus – thus leading to this landmark FDA acceptance.

Rybelsus comes at three doses; 3, 7, and 14 milligrams. Patients should start at 3 mg per day for one month before advancing to the 7 mg, and if needed, to the 14 mg daily dosage. Rybelsus should be taken in an empty stomach, with no more than 4 ounces of plain water, and at least 30 minutes before breakfast.

Similar to other GLP-1 agonists, oral semaglutide can cause gastrointestinal side effects like nausea and diarrhea. Providers should be cautious when prescribing Rybelsus in those with a predisposed risk for pancreatitis, diabetic retinopathy, or kidney injury. It should not be prescribed in people with a personal or family history of medullary thyroid carcinoma.

GT

Primary hyperaldosteronism in obesity

Primary hyperaldosteronism in obesity

In this retrospective study, investigators analyzed a group of 400 adults with hypertension due to primary hyperaldosteronism. The study found that obese patients had smaller aldosterone-producing tumors than lower BMI counterparts. It appears that obese individuals had more aggressive – higher functioning – tumors in spite of their smaller size. Adrenalectomy led to a similar clinical outcome – blood pressure improvement – in patients with or without high BMI. Although these results need to be confirmed, it would be useful for endocrinologists, radiologists, and surgeons to be aware of this phenotype.

GT

Ozempic is superior to Invokana in reducing A1c and body weight

Ozempic is superior to Invokana in reducing A1c and body weight

The Lancets, Diabetes and Endocrinology has just published the results of SUSTAIN 8 clinical trial. The study compared the efficacy and safety of semaglutide 1.0 mg/week versus canagliflozin 300 mg/day in patients with uncontrolled diabetes taking only metformin.

Investigators recruited and followed a group of 800 adults with baseline A1c 7.0-10.5% from 111 centers in 11 countries. They found that the addition of semaglutide to metformin lowered A1c and body weight more than canagliflozin by 0.5% and 2.2 lbs respectively. The trial observed that patients receiving semaglutide experienced higher rates of nausea, while those taking canagliflozin developed more urinary tract infections.

Current ADA and AACE guidelines recommend the use of a GLP-1 agonist or SGLT-2 inhibitor after metformin in uncontrolled type 2 diabetes. Although the study did not compare GLP-1 agonists and SGLT-2 inhibitors as a class, it did suggest initiation of semaglutide 1.0 mg/week over SGLT-2 inhibitors. SGLT-2 inhibitors are regarded to be clinically similar.

An SGLT-2 inhibitor, however, would be a better second-line agent after metformin in diabetes patients with clinical or subclinical heart failure but with proper kidney function (eGFR >45). I anticipate that ADA and AACE guidelines will incorporate SUSTAIN 8 results in their next published standards.

GT

Hypoglycemia due to gastric bypass surgery

Hypoglycemia due to gastric bypass surgery

Obesity and its complications are common, yet on the rise. Subsequently, gastric bypass surgery is on the rise too. Severe hypoglycemia can be a long-term complication of bariatric surgery. The most common method to negate or reduce hypoglycemia is dietary modifications. Patients need to consume small meals of a low glycemic index frequently. Medical therapies with acarbose, diazoxide, and octreotide are often not useful.

Here authors describe the utility of calcium channel blockers (CCBs) in two patients. Difficult to treat hypoglycemia developed in 8 and 13 years after the bypass procedure. Standard approach did not work. Only the use of nifedipine and verapamil improved patient's resistant hypoglycemia. The proposed rationale is that CCBs reduce or delay insulin secretion by pancreatic beta cells.

Although more clinical studies are needed, it is essential to be aware of the potential benefits of CCBs. For some patients with refractory and devastating hypoglycemia, they could be the last resort. Additionally, physicians are already familiar with CCBs as they have been on the market for decades.

GT

Oral "ozempic" lowers A1c and body weight in patients with type 2 diabetes

Oral "ozempic" lowers A1c and body weight in patients with type 2 diabetes

PIONEER 1 was a 26-week randomized clinical trial conducted in nine countries. It tested the efficacy and safety of oral semaglutide vs. placebo in diabetes patients with baseline A1c 8.0%. A group of 703 adults was monitored and analyzed.

At 24 weeks, the higher dose 14 mg of oral semaglutide reduced A1c and body weight by about 1.2% and 5 lbs respectively. Results were statistically significant. Gastrointestinal side effects were more common with semaglutide than placebo but similar to other GLP-1 agonists in the market.

The above results are promising for oral semaglutide to receive FDA approval.

GT

Landmark NIH study: ultra-processed diet increases body weight

Landmark NIH study: ultra-processed diet increases body weight

Common sense and knowledge tell us that whole food is healthier than processed food. It is nice to now have a rigorous randomized clinical trial proving this concept.

The NIH study shows that even when food calories, energy density, macronutrients, sugar, sodium, and fiber were matched, individuals consuming ultra-processed food gained weight compared to those on unprocessed meals.

This is a landmark study as it can influence guidelines/advice at the national level.

GT

New FDA Approval: hydrogel capsule for weight loss

New FDA Approval: hydrogel capsule for weight loss

About 450 overweight or obese adults with BMI 27-40 kg/m2 were randomized to receive Gelesis100 or placebo. Subjects were followed for 6 months. At the end of the trial, patients receiving Gelesis100 lost a significant amount of weight compared to placebo group: about 60% and 25% of the adults lost ≥5% (≥10 lbs) and ≥10% (≥20 lbs) body weight.

Gelesis100 comes in a capsule form. It is taken with plenty of water twice daily before meals. The capsule contains particles, that in the presence of water, have the capability of expanding massively in the stomach, thus triggering a sense of fullness and decreased appetite.

The particles are not absorbed in the bloodstream. No serious adverse events were seen. Gastrointestinal upset was the most common side effect.

GT

More evidence of Metformin benefits in early prediabetes

More evidence of Metformin benefits in early prediabetes

More good news for metformin. MET-REMODEL trial tested patients with known cardiovascular disease and insulin resistance, but without gross diabetes. Patients received metformin or placebo for 12 months.

Compared to the placebo group, subjects receiving metformin experienced the following improvements in 12 months: Less left ventricular mass index,  less LVM, lower systolic BP, decreased body weight and less oxidative stress.

Early start of metformin could be useful in adults with insulin resistance.  Long term side effects of metformin, however, need to be discussed thoroughly with patients.

GT

Victoza use in children with diabetes type 2

Victoza use in children with diabetes type 2

Results of ELLIPSE trial are of major significance as they show that Victoza addition to Metformin helps in further reduction of A1c and fasting plasma glucose. The efficacy and safety appear to be similar as in adults. The most common side effects are gastrointestinal in nature. Based on ELLIPSE trial outcomes, I anticipate broadening of FDA indications for Victoza, to include children and adolescents

GT

Addition of Ozempic to a SGLT2 inhibitor improves hyperglycemia and bodyweight

Addition of Ozempic to a SGLT2 inhibitor improves hyperglycemia and bodyweight

Clinical experience has consistently shown that addition of a GLP-1 agonist to a SGLT2 inhibitor improves hyperglycemia in patients with uncontrolled diabetes. Current study SUSTAIN 9 proves just that for semaglutide, a once weekly injectable GLP-1 agonist.

Addition of semaglutide reduced A1c by 1.4% and bodyweight by 8.4 lbs. Results were statistically significant. As expected, the GI side effects were more pronounced with semaglutide. About 72% of patients were also taking metformin and 13% sulfonylurea.

A group of 300 participants were followed for 30 weeks.

GT

Sexual function after bariatric surgery

Sexual function after bariatric surgery

This meta-analysis shows that bariatric surgery significantly improves sexual function in men but that a more limited degree of improvement is achieved in women.

In obese male patients who underwent bariatric surgery, the levels of the sex hormones TT, FT, LH, FSH, and SHBG significantly increased, and the level of E2 decreased. In obese female patients, the levels of the sex hormones TT, FT, and E2 decreased, but the levels of LH, FSH, and SHBG increased.

Future studies should be performed to elucidate the mechanism of the improved sexual function in obese patients after bariatric surgery. 

JES

A possible new drug for diabetes and obesity (PTP1b inhibitor)

A possible new drug for diabetes and obesity (PTP1b inhibitor)

Protein tyrosine phosphatase 1B (PTP1b) was first discovered in 1988. It is a counter-regulator to insulin and leptin signaling pathways. Given current endemic of insulin resistance via obesity and type 2 diabetes, it is natural to search for drugs that improve insulin and leptin sensitivities. PTP1b suppression is one of those options.

Here is a phase 2 clinical trial on an antisense inhibition of PTP1b (IONIS-PTP-1BRx). Results are promising but not profound: A1c and body weight dropped by 0.7% and 6 lbs in 27 to 36 weeks. No major adverse events were seen. A clearer picture of the drug will emerge in the future trials. At the same time the search for the other perfect PTP1b continues.

GT

Leptin improves brain insulin resistance

Leptin improves brain insulin resistance

Leptin deficiency leads to weight gain, obesity, and insulin resistance. Leptin replacement in the form of metreleptin has been approved by the FDA for congenital or acquired generalized lipodystrophy. The current analysis reveals that metreleptin also improves central insulin sensitivity primarily via hypothalamus and to a lesser extent prefrontal cortex.

GT

BMI vs. CVD contradiction

BMI vs. CVD contradiction

The study observes that higher BMI is associated with higher cardiovascular mortality and morbidity. On the contrary, it is intriguing to see that CVD longevity is prolonged in adults with elevated BMI (>25) compare to those with normal BMI (19-25). A speculative explanation could be that once cardiovascular illness has been established, the high BMI-induced damage is irreversible and subsequently somewhat protective. Future research will clarify the molecular mechanisms of these observations.

GT

Diabetes and obesity increase the risk of 12 malignancies

Diabetes and obesity increase the risk of 12 malignancies

The article provides more evidence that diabetes and obesity increase the risk of malignancy, particularly of colorectal, gallbladder, pancreas, kidney, liver, endometrial, postmenopausal breast, ovarian, gastric cardia, thyroid cancer, esophageal adenocarcinoma and multiple myeloma. It is estimated that 430 million adults have diabetes worldwide, while 2.0 billions are overweight or obese. How could this global health problem be meaningfully approached?

GT

Bariatric surgery improves mortality outcomes

Bariatric surgery improves mortality outcomes

Bariatric surgery using laparoscopic banding, gastric bypass, or laparoscopic sleeve gastrectomy, compared with usual care nonsurgical obesity management, was associated with lower all-cause mortality over a 4.5 years follow-up.

JAMA

Obesity and kidney disease

Obesity and kidney disease

This is a nice review showing how obesity contributes to kidney disease, particularly in the setting of metabolic syndrome, diabetes and hypertension.

The process starts with glomerular hyperfiltration, and made worse by high sodium and animal protein intake. I suspect that inflammation from visceral adiposity plays a major role too.

It appears that the risk for kidney disease accumulates over time, as prognosis is worse in childhood-onset vs. adult-onset obesity.

GT

Obesity, from childhood to adulthood

Obesity, from childhood to adulthood

The study predicts dim outcomes. Around 57% of today's children are expected to be obese by age 35. High BMI and particularly high waist circumference are well known contributors to inflammation, insulin resistance, diabetes, high blood pressure, metabolic syndrome and malignancy.

Can it be delayed, reversed, stopped? If so, how? Education?

GT

Joint statement on metabolic surgery for diabetes

Joint statement on metabolic surgery for diabetes

Below are listed recommendations on when to consider metabolic surgery for type 2 diabetes. Decisions making would depend on BMI severity and glycemic control.

The joint statement advises surgery for patients with class III obesity, and in those with class II but have high A1c. Consideration should be given to adults with controlled class II or uncontrolled class I obesity. 

Standards are listed below with a slightly modified wording for easier and succinct reading:

GT