Articles

Bisphosphonate infusion for osteopenia

Bisphosphonate infusion for osteopenia

A group of 2,000 women with osteopenia receiving either zolendronate infusion or placebo were followed for 6 years. Zoledronate 5 mg or placebo were provided every 1.5 years. At the end of the study, the intravenous bisphosphonate reduced vertebral and nonvertebral fractions significantly by about 55% and 35% respectively.

Findings are of major significance as bisphosphonates in general and zolendronate specifically have been approved only for osteoporosis and not osteopenia. Would this expand indications for zoledronate? Should patients with osteopenia be treated or monitored?

GT

Invokana protects the heart and kidneys

Invokana protects the heart and kidneys

Patients with type 2 diabetes receiving Invokana experienced 30% and 20% lower rates of kidney disease progression and cardiovascular events respectively, when compared to the placebo group.

Results were so obvious and significant that the study was terminated early. About 4500 subjects with DM2 were followed for about 2.5 years. No increased rates of fractures or amputations were seen with Invokana.

GT

Metformin found to be safe during pregnancy

Metformin found to be safe during pregnancy

The study found no major adverse events of metformin during pregnancy. This is good news as metformin is an important intervention for hyperglycemia of pregnancy. The following birth outcomes were assessed: cesarean section, neonatal weight, and serious neonatal adverse events.

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

2019 Endocrine Society Guidelines: diabetes approach in older adults

2019 Endocrine Society Guidelines: diabetes approach in older adults


The Endocrine Society has just released its guidelines on how to manage the elderly with diabetes. Guidelines are overall similar to those of ADA and AACE but with greater emphasis in avoidance of adverse events such; as hypoglycemia, malnutrition, excessive weight loss, frailty, falls, and drug side effects. See below for more details.

GT

New FDA Approval: romosozumab for osteoporosis

New FDA Approval: romosozumab for osteoporosis

Romosozumab , brand name Evenity, has now been approved by the FDA as a viable option for patients with advanced osteoporosis.

Romosozumab is a monoclonal antibody that specifically inhibits sclerostin. The approval comes with a major black box warning as the sclerostin inhibitor elevates the risk of heart attack, stroke and cardiovascular deaths.

Prior to Evenity initiation, patients need to be screened carefully for background cardiovascular disease. As the prevalence of both CVD and osteoporosis increases with age, the most likely candidates for such a therapy would be those at the highest risk for fragility or compression fractures.

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

2019 AACE Guidelines: Diabetes Type 2 principles

2019 AACE Guidelines: Diabetes Type 2 principles

AACE standards were published in January 2019. They are a continual update of the original 2013 guidelines. Unlike ADA which recommends a general A1c target ≤7.0%, AACE promotes a tighter A1c goal of ≤6.5% for most patients with type 2 diabetes.

Recommendations also address lifestyle interventions, obesity, prediabetes, hypoglycemia, hypertension and dyslipidemia. Oral and injectable medications including insulin are discussed. A key priority is the avoidance of hypoglycemia — do no harm!

GT

Addition of PCSK9 inhibitor Alirocumab further lowers CVD events.

Addition of PCSK9 inhibitor Alirocumab further lowers CVD events.

In ODYSSEY trial, the addition of PCSK9 inhibitor, Alirocumab to high-intensity statin further reduced cardiovascular events by 15% in patients with very-high baseline CVD risk (prior ACS) and elevated atherogenic cholesterol particles. Atherogenicity was defined by LDLc ≥70 mg/dL, non-HDLc ≥100 mg/dL, or Apo B ≥80 mg/dL.

About 19,000 patients with acute coronary syndrome 1-12 months prior to study initiation were followed for 3 years. The study target was final LDLc between 25-50 mg/dL. Similar to FOURIER 2017 results, ODYSSEY 2018 adds more evidence to the notion “the lower the LDLc, the lower ASCVD events”

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

New FDA approval: oral testosterone

New FDA approval: oral testosterone

In March 2019 FDA approved the first oral testosterone supplementation for male patients with documented central (primary) or peripheral (secondary) hypogonadism. The medication is given twice a day orally. The recommended starting dose is about 250 mg every 12 hours. The minimum dose is about 150 mg BID with a maximum dose of 400 mg BID.

Follow up blood work needs to be done at least 7 days after initiation and 6 hours after the morning dose. Side effects may include elevated blood pressure, increased red blood cell mass, prostate enlargement, and GI upset. The approval comes with a black box warning for increased risk of hypertension and cardiovascular events.

GT

Thyroid cancer: low-dose radioactive iodine works in the long term too

Thyroid cancer: low-dose radioactive iodine works in the long term too

Now we have long-term data from the original HiLo trial. Patients with no distant metastasis, well-differentiated thyroid carcinoma do as well with low-dose radioactive iodine (30 mCi) treatment compared to those receiving the high dose RAI (100 mCi).

Unless distant metastasis is documented, patients with well-differentiated papillary or follicular cancer should receive 30 mCi I-131 when indicated. A group of 450 patients was followed for about 7 years.

GT

Risk factors control is also important in type 1 diabetes

Risk factors control is also important in type 1 diabetes


This major observational study shows that the tight control of risk factors is associated with much lower rates of cardiovascular events and total mortality in patient with type 1 diabetes. Such factors are hyperglycemia, systolic blood pressure, protein in the urine, and the “bad” cholesterol (A1c, sBP, McAlb, LDLc).

This association has already been seen in adults with type 2 diabetes. For a practitioner, this study calls for a tight control of the above risk factors in patients with type 1 diabetes as in those with type 2. A group of 30,000 DM1 individuals were followed for about 10 years

GT

Red raspberries for breakfast

Red raspberries for breakfast

This simple study shows that frozen red raspberries in quantities of 125-250 mg (1-2 cups), when taken with a typical high-carb breakfast, improve insulin resistance in adults with prediabetes. Although these results would need to be validated, having red raspberries for breakfast sounds just right.

GT

Incidence of Cushing's disease is on the rise

Incidence of Cushing's disease is on the rise

The study finds that the incidence of pituitary Cushing is still rare but increased over the past 30 years. Its current incidence is estimated to be 2.0 cases/million/year. However it is unknown if this increase is real or due to improved physician awareness and biochemical testing.

GT

Thyroid supplementation in heart failure

Thyroid supplementation in heart failure

This 5-year observational study shows that thyroid hormone supplementation increases major adverse cardiovascular events (MACE), cardiovascular death, and all-cause mortality in patients with heart failure. Indirectly, this is in accordance with the well-documented benefits of beta-adrenergic receptor blockade in persons with cardiac failure.

Clinically, in patients with concomitants hypothyroidism and heart failure, thyroid hormone supplementation should be started at a low dose, increased slowly, and aiming a higher TSH target than in general population.

GT

The lost Woltman’s Sign of Hypothyroidism

The lost Woltman’s Sign of Hypothyroidism

A nice academic demonstration of the Woltman’s sign in a patient with profound hypothyroidism, who’s TSH was 200 mIU/L. Delayed relaxation of the ankle reflex normalized as TSH improved with proper thyroid hormone supplementation. The Woltman’s sign could be useful if thyroid laboratory testing is not available and the patient’s baseline ankle reflex is known.

GT

Oral insulin 338 is effective but expensive

Oral insulin 338 is effective but expensive

This short phase 2 clinical trial shows that the oral insulin 338 improves fasting plasma glucose similar to the long-acting insulin glargine. Hypoglycemia rates are also similar. However, further studies of the oral insulin 338 are halted due to its need for high doses and cost. A group of 50 patients were followed for 8 weeks. The quest for the first oral insulin, nonetheless, continues.

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

Vascepa (fish oil) reduces ischemic cardiovascular events in high risk patients

Vascepa (fish oil) reduces ischemic cardiovascular events in high risk patients

The current study is of a major clinical significance as it shows that EPA lowers ischemic cardiovascular events by 25% in high rick CVD patients who are already receiving statin therapy. The EPA treated patients, however, experienced more hospitalizations for atrial fibrillation and a higher propensity for serious bleeding than placebo. Findings are remarkable as they come from a major randomized clinical trial (IMPROVE IT). About 8,000 patients were followed for 5 years.

This outcome data is in accordance with established observation and notion that hypertriglyceridemia is an independent risk factor for cardiovascular disease, mainly via increased inflammation and concentration of the non-HDL cholesterol. Prior clinical studies have also shown that EPA lowers non-HDL cholesterol more than DHA.

Omega-3s, EPA and DHA, are two key ingredients of fish oil. A stable and pure form of EPA has been FDA approved for very high serum triglyceride >500 mg/dL since 2012. It is marketed under the brand-name vascepa. Lovaza, a mixture of EPA and DHA, has also been approved by FDA since 2004 for severe hypertriglyceridemia.

I anticipate that in the future NLA, ACC/AHA, AACE and ADA guidelines will reflect and incorporate the current findings of IMPROVE IT.

GT