"Metreleptin Treatment Leads to Long-Term Improvements in Diabetes and Lipid Control in Patients with Lipodystrophy"

RESULTS from a new analysis of an ongoing, long-term research study of the investigational drug metreleptin, an analog of the human hormone leptin, demonstrated robust reductions in HbA1c levels and triglycerides that were sustained for several years of treatment in patients with lipodystrophy.

Lipodystrophy

“Lipodystrophy is a rare, debilitating chronic disease with a large, unmet clinical need. No therapies are indicated specifically for the treatment of the metabolic abnormalities associated with lipodystrophy,” Christian Weyer, MD, senior vice president, research and development, Amylin Pharmaceuticals, said at a late-breaking oral session on April 17 at the 20th Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinologists (AACE) in San Diego.

In the study, which has been ongoing for more than 10 years, researchers at the NIH are examining the effects of metreleptin on several metabolic abnormalities, such as diabetes and hypertriglyceridemia, in patients with rare inherited or acquired forms of lipodystrophy.

[Amylin recently submitted the clinical and nonclinical sections of a rolling Biologics License Application (BLA) for metreleptin to treat diabetes and/or hypertriglyceridemia (high levels of triglycerides in the bloodstream) in patients with rare inherited or acquired forms of lipodystrophy. If approved, metreleptin would be the first therapy indicated specifically for the treatment of diabetes and high triglycerides in patients with lipodystrophy, and the first approved therapeutic use of leptin.]

Weyer presented results of an analysis of 55 patients with lipodystrophy who were assigned to metreleptin. According to the researchers, this is the largest cohort to date. At baseline, 75% of patients had uncontrolled diabetes (HbA1c ≥7%) and 75% had hypertriglyceridemia (≥200 mg/dl).

“When metreleptin was introduced as a subcutaneous injection once or twice a day, both HbA1c and triglycerides fell very rapidly and profoundly in the first 4 months of therapy,” Weyer said. When patients were followed to 3 years, the changes were maintained. In the patients with diabetes, mean HbA1c decreased from 9.4% at baseline to lower than 7% at year 3. In the patients with hypertriglyceridemia, mean triglyceride concentrations decreased from 500 mg/dl to under 200 mg/dl at year 3.

Weyer said adverse events were consistent with known comorbid conditions of lipodystrophy, including pancreatitis, proteinuria and autoimmune/chronic hepatitis, or expected pharmacological effects of metreleptin, such as weight loss or insulin-induced hypoglycemia in the setting of improved insulin sensitivity in patients taking high doses of insulin.

Other studies conducted worldwide have demonstrated metreleptin’s positive effects on insulin sensitivity, high triglycerides, hyperglycemia and liver fat in patients with lipodystrophy who are not responsive to conventional lipid and glucose-lowering agents, the researchers said. Amylin is working with the FDA to get approval of metreleptin. If approved, it would be the first therapy indicated specifically for the treatment of diabetes and hypertriglyceridemia in patients with lipodystrophy.

Commenting on Weyer’s remarks, AACE President Elect Yehuda Handelsman, MD, said:

This whole thing about leptin is fascinating, and I think there is so much more to learn about it. (News about) leptin is everywhere: it is related to bone, it turns out, it is related to smell, taste and hunger. We found out from Dr. Unger (here at the meeting) that it suppresses glucagon terrifically.

Dr. Weyer represents an organization that has a drug called exenatide (Byetta), a glucagon-like peptide 1 that we also think in some way suppresses glucagon. It will be interesting to know if there is any relationship between the leptin suppression and glucagon suppression. We can see now that leptin, in the rarest disease, may be more applicable to a larger group of people that may have partial lipodystrophy, and we don’t as yet know how to recognize it.

Drugs Cannot Treat The Underlying Cause of Diabetes!

If you or someone you know is diabetic and taking medication for it, please understand that you cannot successfully treat the underlying cause of diabetes with drugs.

Avandia - the controversial drug that is linked to increased incidents of heart attacks (see my earlier posts) - works by making diabetes patients more sensitive to their own insulin, helping to control blood sugar levels.

In fact, most conventional treatments for type 2 diabetes utilize drugs that either raise insulin or lower blood sugar. Avandia, for example, lowers your blood sugar levels by increasing the sensitivity of liver, fat and muscle cells to insulin.

But you must understand that diabetes is NOT a blood sugar disease you may have been led to believe.

Type 2 diabetes is actually a disease caused by insulin resistance and faukty leptin signalling, both of which are regulated through your diet.

Conventional treatment, which is focused on fixing the symptom of elevated blood sugar rather than addressing the underlying disease, is doomed to fail in most cases.

Type 2 diabetes is virtually 100 percent avoidable, and can be effectively treated without medications in about the same percentage of cases.

Leptin, a relatively recently discovered hormone produced by fat, tells your body and brain how much energy it has, whether it needs more (saying "be hungry"), whether it should get rid of some (and stop being hungry) and importantly what to do with the energy it has (reproduce, upregulate cellular repair, or not).

In fact, the two most important organs that may determine whether you become (type 2, insulin resistant) diabetic or not are your liver and your brain, and it is their ability to listen to leptin that will determine this.

How is this done?

Well, that's the kicker. The only known way to reestablish proper leptin and insulin signaling is through a proper diet and exercise!

There is NO drug that can accomplish this, but following these simple guidelines can help you do at least three things that are essential for successfully treating diabetes: recover your insulin/leptin sensitivity, help normalize your weight, and naturally normalize your blood pressure.

As an aside, none of these will drastically raise your risk of a heart attack the way Avandia will … and in fact will have only positive benefits on your heart and your entire body:

• Severely limit or eliminate sugar and grains in your diet, especially fructose which is far more detrimental than any other type of sugar.Finding out your nutritional type will help you do this without much fuss. While nearly all type 2 diabetics need to swap out their grains for other foods, some people will benefit from using protein for the substitution, while others will benefit from using more vegetable-only carbohydrates. Therefore, along with reducing grains and sugars, determining your nutritional type will give you some insight into what foods you should use to replace the grains and sugars.
• Exercise regularly -- a must for anyone with diabetes or pre-diabetes. Typically, you'll need large amounts of exercise, until you get your blood sugar levels under control. You may need up to an hour or two a day. Naturally, you'll want to gradually work your way up to that amount, based on your current level of fitness.
• Avoid trans fats
• Get plenty of omega-3 fats from a high quality, animal based source.
• Get enough high-quality sleep every night.
• Optimize your Vitamin D levels. Recent studies have revealed that getting enough vitamin D can have a powerful effect on normalizing your blood pressure and that low vitamin D levels may increase your risk of heart disease.
• Monitor your fasting insulin level. This is every bit as important as your fasting blood sugar. You'll want your fasting insulin level to be between 2 to 4. The higher your level, the worse your insulin receptor sensitivity is.

So please remember that a drug will never treat the underlying cause of type 2 diabetes the way these lifestyle changes will.

It looks like Avandia is set to go the way of Vioxx, which was also pulled from the market after killing 60,000 people. You don't need to wait for the red tape to be removed to start looking out for your own health.

(Adapted from an article in Mercola.com)