What’s New in Medicine

This week’s news comes from the April 17, 2017 issue of the Journal of the American Medical Association.
The article’s title is quite a mouth full:

“Association Between Use of Sodium-Glucose Cotransporter 2 inhibitors, Glucagon-Like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors with All-Cause Mortality in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis.”

Let’s break this down and see what it says.

Diabetes Mellitus is a disease which affects a growing percentage of our country. There are two kinds of Diabetes.

  • Type 1 or Insulin Dependent Diabetes Mellitus (IDDM)is a disease whereby the body makes antibodies against the cells which make insulin. Therefore, the body cannot make any insulin. It is necessary to inject insulin to control blood sugar. This condition is not as common as Type 2 Diabetes.
  • Type 2 diabetes, or non-Insulin Dependent Diabetes Mellitus (NIDDM) the body is resistant to insulin. The pancreas must make more and more Insulin to control blood sugar. Eventually the pancreas cannot make enough and then the blood sugar rises out of control. Many hormones which control glucose. These hormones include:
    • Insulin: causes cells to take up glucose and lowers blood glucose
    • Glucagon causes the liver to make more glucose
    • GLP1 is made in the intestinal track when we eat. It causes the pancreas to make more insulin and less glucagon.
    • SGLT-2 is a protein which causes the kidney to save glucose. If this is inhibited, the kidney excretes glucose into the urine.

There have been several classes of medicine to treat Type 2 Diabetes. This article reports on three classes of medications. The authors found 236 high quality trials. The data from all of them were combined. The question was “How well do these medications work.” The medications were compared to each other, or to a placebo, or to no treatment.

The three classes studied were:

1 Sodium Glucose Cotransporter 2 Inhibitors. (SGLT-2 Inhibitors). These medications inhibit the kidney from saving as much blood sugar as possible. The kidney therefore puts more blood sugar in the urine – about 500 calories each day. That amounts to a pound of weight each week.

2. Glucagon-like Peptide 1 Agonists. (GLP1 Agonists). This medication has a structure like glucagon but has a very different effect. GLP1 is a hormone which is made in the intestines when we eat. It stimulates the pancreas to make more insulin and less glucagon. It also slows gastric emptying. This medication binds to the same receptor that GLP1 does and lasts much longer.

3. Dipeptidyl Peptidase 4 Inhibitors (DPP4 Inhibitor) block the degradation of the GLP1 hormone which is made when we eat. Thus, the GLP1 hormone is not broken up into inactive parts as rapidly as it normally is. The GLP1 hormone lasts longer and thereby causes the effect of the hormone to make more insulin and less glucagon in the pancreas. More insulin decreases the amount of blood sugar; less glucagon decreases the amount of blood sugar that is made by the liver.

Each class works. What happened to the patients who took one of these medications

Medication Result

The primary outcome studied was all cause mortality. This was the percent of patients who died for any reason. It included medical and well as non-medical causes, such as accidents.
Each class was better than the control (those taking either a placebo or taking nothing.
The SGLT2 Inhibitors appear to reduce death the most, but the differences are small.

There were several secondary outcomes: See below the reference for these categories.

  1. Cardiovascular death includes death resulting from an acute myocardial infarction, sudden cardiac death, death due to heart failure, death due to stroke, and death due to other cardiovascular causes.
  2. The next secondary outcome was all patients who had a heart attack, both those died and those who did not.
  3. Another secondary outcome was the number of patients who developed heart failure.
  4. Stroke was the percent of patients who suffered a stroke of any kind.

In every category studied, each of the medications made diabetic control better. In some of the cases the change was small, but always better.

Over the last several years, a number of new ways to treat diabetes have become available. It is a major change, giving the medical profession new ways to help the diabetic patient. If you have diabetes, I would recommend that you join the American Diabetes Association. They are a wonderful resource for information. Talk with your doctor about the best way for you to control your medical situation.

Richard B. Johnson, Jr.
Ph.D., M.D., F.A.C.P.

Abbreviations:
DPP4-I Dipeptidyl Peptidase 4 Inhibitor
GLP1-A Glucagon-Like Peptide 1 Agonist
SGLT-2 Sodium glucose cotransporter 2

Examples of Medications:
Trade Name – Chemical Name
DPP4-I
Januvia – Sitagliptin
Galvus- Vildagliptin
Onglyza- Saxagliptin
Tradjenta- Linagliptin

GLP1
A Byetta, Bydureon- Exenatide
Victoza, Saxenda- Liraglutide
Trulicity- Dulaglutide
Ozempic- Semaglutide

SGLT-2-2
Invokana- Canagliflozin
Farxiga – Dapagliflozin
Jardianc- Empagliflozin

References:

JAMA.2018:319(15): 1580-1591. doi:10.1001/jama 2018 3024
https://jamanetwork.com/journals/jama/fullarticle/2678616

Standardized Definitions for End Point Events in Cardiovascular Trials
www.clinpage.com/images/uploads/endpoint-defs_11-16-2010.pdf