Combo Therapy May Effectively Control Diabetes in Prader-Willi Patients, Case Study Shows

Combo Therapy May Effectively Control Diabetes in Prader-Willi Patients, Case Study Shows

Patients with Prader-Willi syndrome (PWS), diabetes, and fat accumulation in the pancreas may benefit from a combined treatment of two therapies that treat diabetes: tofogliflozin (which has not yet been approved in the U.S.) and dulaglutide, according to a Japanese case report.

The study, “Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitor as an Add-on Drug to GLP-1 Receptor Agonists for Glycemic Control of a Patient with Prader–Willi Syndrome: A Case Report,” was published in the journal Diabetes Therapy.

One of the most serious consequences of Prader-Willi syndrome is obesity, caused by excessive eating, the patient’s inability to feel full, a slower metabolism, and a low expenditure of energy. Most physical problems related to PWS are a consequence of obesity.

Severe obesity is known to increase the risk of developing diabetes, but controlling blood sugar through diet is difficult for Prader-Willi patients due to their tendency to eat more than they should and to experience behavioral disorders. Treating diabetes in these patients normally involves insulin or other injected or oral medicines.

The case study is about a 36-year-old Japanese man, diagnosed at the age of 10 with Prader-Willi. At 16, he was severely obese and was diagnosed with diabetes. He then started to take several medicines to help control his blood sugar levels.

Starting at age 28, he received the oral medicines glibenclamide, metformin, or pioglitazone, but none led to improvements in hemoglobin A1C levels — an measure of blood sugar levels — which remained excessively high.

Then, treatment with metformin, miglitol, and NPH insulin, combined with dietary and exercise therapy, led to the patient dropping 26.5 pounds, but they were ineffective in reducing his blood sugar levels.

Despite substituting NPH insulin with other treatments, including GLP-1 receptor agonists (a class of drugs used in the treatment of diabetes), the patient’s body weight continued to drop sharply so that he lost 61.7 pounds, but his sugar levels remained high.

At age 35, clinicians began treating the Prader-Willi patient with tofogliflozin, an SGLT2 inhibitor, and the GLP-1 RA (receptor agonist) dulaglutide.

According to the team, tofogliflozin seemed to be the only therapy that was effective in controlling the patient’s blood sugar levels. Right after starting the treatment, his sugar levels began to drop, from about 11% to 8.5% nine months after, while his body weight was kept stable.

An abdominal examination by computer tomography scans revealed that the patient’s subcutaneous fat mass was significantly reduced, but the accumulation of fat in his organs did not decrease as readily.

Also, clinicians saw reduced fat infiltration in the pancreas, where previous high levels indicated the presence of non-alcoholic fatty pancreas diseaseNo significant changes were detected in the liver. 

The findings indicate the benefits of a combined therapy of a GLP-1 receptor agonist (in this case, dulaglutide) and an SGLT2 inhibitor (tofogliflozin), when patients do not respond to more standard treatments. These therapies have several complementary features involving the way they work.

“While the elimination of glucose through the urine caused by SGLT2 inhibitors [tofogliflozin used] may stimulate appetite, this effect may be offset by the appetite-suppressing effect of GLP-1RAs [dulaglutide used] that mitigates the deleterious effects of any weight gain,” researchers wrote.

“These drugs may therefore improve glycemic control, body weight, and cardiovascular risk when they are administered together,” they added.

An additional benefit seen with this combination therapy was that they stopped muscle mass loss.

According to the team, it is not possible to say if the improvement of fatty pancreas was a cause or an effect of the control of blood sugar levels.

Researchers concluded that this case report clearly supports the effectiveness of combining SGLT2 inhibitors with GLP-1RAs for the treatment of Prader-Willi patients and non-alcoholic fatty pancreas disease.

The team advises, however, that if this treatment approach is selected, “medical staff should be instructed not to administer a low-carbohydrate diet when SGLT2 inhibitors are used in PWS,” as this may lead to severe ketoacidosis — a life-threatening condition where the liver starts to break down fat excessively fast.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.
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Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.
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