Leo Robert

If left uncontrolled, type 2 diabetes mellitus (T2DM) can result in serious complications. Improved glycemic control reduces their onset and progression, but close to half of adults who have T2DM do not achieve levels of glucose control recommended by the American Diabetes Association.

While the search goes on for novel therapeutic agents to improve glycemic control in patients with T2DM, the use of sodium glucose co-transporter-2 (SGLT2) inhibitors in combination with other agents has emerged as a promising treatment option.

Three combination SGLT2 products have been FDA-approved within the past 6 months. Find key points about each of these new agents on the pages that follow.

Glyxambi Is the Only SGLT2 and DPP-4 Combo

Glyxambi (empagliflozin and linagliptin), an SGLT2 inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination for the treatment of adults with T2DM, was FDA-approved in February 2015.

• Glyxambi is currently the only prescription medication in the United States that combines the mechanisms of action of SGLT2 and DPP-4 inhibitors to improve glycemic control as an adjunct to diet and exercise.

• A phase 3 clinical trial evaluated the efficacy and safety of Glyxambi (10/5 mg and 25/5 mg) compared with the individual components (empagliflozin, 10 mg or 25 mg; linagliptin, 5 mg) in 686 adults with T2DM who were also taking high-dose metformin.

• As an add-on to metformin, Glyxambi showed statistically significant reductions in A1c level compared with empagliflozin and linagliptin alone at 24 weeks.

• Empagliflozin/linagliptin was well tolerated. The most common adverse effects include urinary tract infections, stuffy or runny nose and sore throat, and upper respiratory tract infections.

• Glyxambi is not recommended in patients with type 1 diabetes mellitus or those with diabetic ketoacidosis. It should not be taken by patients with severe renal impairment, end-stage renal disease, or dialysis or a history of hypersensitivity reaction to linagliptin or of serious hypersensitivity reaction to empagliflozin.

• Although Glyxambi is not approved for weight loss, it provided significant reduction in weight at 24 weeks compared with linagliptin alone.

Dapagliflozin, Metformin Combined in Xigduo XR

Xigduo XR (dapagliflozin and metformin hydrochloride) extended release, a combination of an SGLT2 inhibitor and a biguanide for patients with T2DM, received FDA approval in October 2014.

• The FDA approved once-daily Xigduo XR based on 4 phase 3 clinical trials. The trials provided clinical evidence for efficacy and safety in treatment-naive patients and in patients inadequately controlled on metformin and compared with a sulfonylurea (glipizide) plus metformin.

• This is the first US approval for a once-daily tablet that combines an SGLT2 inhibitor and metformin HCl extended release-antihyperglycemic agents with complementary mechanisms of action.

• This combination is indicated as an adjunct therapy to diet and exercise to improve glycemic control in adults with T2DM when treatment with both dapagliflozin and metformin is appropriate.

• Xigduo XR was already approved in Australia for adults with T2DM, and Xigduo (dapagliflozin and metformin hydrochloride), which uses an immediate-release form of metformin, is approved in the European Union.

• Xigduo XR is approved with multiple dosage strengths of dapagliflozin and metformin HCl extended release, respectively, including 5 mg/500 mg, 5 mg/1000 mg, 10 mg/500 mg, and 10 mg/1000 mg.

• Xigduo XR should be taken once daily in the morning with food with gradual dose escalation to reduce the risk of GI adverse effects caused by metformin.

Invokamet: An SGLT2 Inhibitor With Metformin

 Invokamet (canagliflozin and metformin hydrochloride) is an SGLT2 inhibitor and biguanide combination indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM who are not adequately controlled on a regimen containing metformin or canagliflozin or in patients already being treated with both canagliflozin and metformin. The drug received FDA approval in August 2014.

• Invokamet is the first fixed-dose combination of an SGLT2 inhibitor with metformin approved in the United States.

• The co-administration of canagliflozin and metformin has been studied in 6 phase 3 clinical studies that enrolled 4732 patients who had T2DM. The studies evaluated canagliflozin in combination with metformin compared with metformin alone and with metformin plus another DM therapy.

• The combination lowered blood sugar and, in prespecified secondary end points, was associated with significant reductions in body weight and systolic blood pressure.

• Invokamet should not be used in patients with type 1 DM or for diabetic ketoacidosis. The prescribing information also contains a boxed warning for lactic acidosis.

• Potential serious adverse effects include dehydration, kidney problems, hyperkalemia, liver problems, and hypoglycemia.

• Invokamet is available in tablets containing canagliflozin, 50 mg or 150 mg, and metformin, 500 mg or 1000 mg. The recommended dosing is twice daily.

• The use of SGLT2 inhibitors in combination with other agents has emerged as a promising therapeutic option for patients with T2DM.

• Glyxambi is the only prescription medication in the United States that combines SGLT2 and DPP-4 inhibitors to improve glycemic control as an adjunct to diet and exercise.

• The approval of Xigduo XR is the first in the United States for a once-daily tablet that combines an SGLT2 inhibitor and metformin HCl extended release.

http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Glyxambi/Glyxambi.pdf

http://www.azpicentral.com/xigduo/pi_xigduoxr.pdf

http://www.janssenprescriptionassistance.com/invokamet-cost-assistance

Articles

The use of SGLT2 inhibitors in combination with other agents to improve glycemic control has emerged as a promising therapeutic option.

Combo SGLT2 Inhibitors Double Down on Diabetes

Most patients with type 2 diabetes evenutally require insulin to manage hyperglycemia and insulin intensification is the norm as beta cell function continues to decline. Prescribing insulin effectively is nuanced medicine. These 5 slides look at signs your patient is ready for insulin, and research on reduced risk of nocturnal hypoglycemia, GLP-1 agonists with basal insulin, obesity and response to biphasic insulin 50/50, and the pros and cons of premixed vs multidose insulin.

Slideshows

Optimizing the use of insulin for treatment of hyperglycemia in patients with diabetes is an ongoing research endeavor. Here, several recent developments you should know about. 

Inside Insulin: 5 Sets of Facts, Figures, and Findings

Premixed insulin pros and cons, drugs and renal impairment, thumbs up for eating tree nuts, a new GI microbiome modulator, mental health coaching eases depression and blood sugar level. The 5 summaries below offer research and literature highlights to keep you up-to-date with scientific advances and new diagnosis and treatment options.

• Use of a premixed insulin product can help ease anxiety for patients and physicians, but it’s not appropriate for all patients who require insulin.

• Premixed insulin therapy tends to be most successful for patients who lead a relatively routine lifestyle with 3 daily meals taken at regular times and with similar carbohydrate content.

• In a consistent, predictable lifestyle, premixed insulin requires fewer daily injections than multidose insulin therapy and maintains reasonably good glycemic control.

• The premixed product can be human insulin or analog. Human insulin may be associated with more hypoglycemia. Analog insulin offers the convenience of meal-time administration, superior postprandial control, and less nocturnal hypoglycemia.

• The patient needs to be part of the decision-making team about choice of insulin product.

2. Diabetes drugs account for renal impairment

• Chronic kidney disease can complicate treatment for type 2 DM, especially when available noninsulin therapies are considered.

• Clinicians should be aware of the concerns and consequences when the current type 2 DM therapies are used in patients with renal impairment and consider discontinuation or dose reduction.

• The DPP-4 inhibitors may be a safe and effective alternative in these patients, especially linagliptin.

3. Tree nuts for type 2 DM: surveys say, go nuts!

• Two recent studies supported recommendations to consume tree nuts alone or as part of heart healthy dietary patterns-such as the Mediterranean, Portfolio, Vegetarian and DASH dietary patterns-to improve glycemic control in patients with type 2 DM.

• Study authors note that results could be explained by an overall shift to a healthier eating pattern in which nuts displace foods high in saturated fat or carbohydrates with a high glycemic index.

• Making healthier choices, and educating your patients on how to do it, at the very least “does not harm.”

4. A new GI microbiome modulator shows promise for DM

• The modulator improved oral glucose tolerance in patients with prediabetes in a pilot study.

• NM504, the first in a new class of GI microbiome modulators, improved serum glucose levels during an oral glucose tolerance test compared with placebo.

• Insulin levels were similar between groups.

• The drug also decreased the desire to eat and may improve treatment for type 2 DM.

5. Mental health coaching eases depression and blood sugar levels

• In a pilot study, patients with a new diagnosis of DM were referred to a certified diabetes educator (CDE); patients with depression received mental health coaching.

• Anxiety and depression scores and A1C levels decreased.

• “Those who had mental health coaching said it was life-changing, life-saving, and helped them feel better and happier than they had in a long time,” said Melissa Herman, RD, a certified diabetes educator.

Use these 5 brief summaries of recent developments in the study of diabetes and trends in diabetes care to stay current and optimize care for your patients.

5 More Clinical Pearls to Continue Your Diabetes Education

A dramatic increase in nonalcoholic fatty liver disease; gastrectomy outperforms medical care in diabetes mellitus; a diabetes-pancreatic cancer link. . .Â  new information about diabetes is being discovered at a rapid pace.The 5 slides here provide highlights of recent studies and - offer a variety of practical pointers and information that can be put to use in your practice.

The 5 slides here provide highlights of recent studies of diabetes and - offer a variety of practical pointers and information that can be put to use in your practice.

Continuing Your Diabetes Education: 5 Clinical Pearls

Diabetes mellitus (DM) education significantly improves outcomes among patients who have the condition, leading to reduced blood sugar, blood pressure, and cholesterol levels.

This according to data to be presented by the Diabetes Self-Management Education Program from New York-Presbyterian Hospital today at AADE14, the American Association of Diabetes Educators Annual Meeting & Exhibition, taking place August 6-9 in Orlando.

In the study, 1263 patients with DM living in a low-income urban area with a high immigrant population received four 30-minute one-on-one sessions with DM educators to learn about and work on the AADE7

 Self-Care Behaviors: (1) healthy eating, (2) being active, (3) monitoring, (4) taking medication, (5) problem solving, (6) healthy coping, and (7) reducing risks. In addition, the paatients participated in group sessions with DM educators to help them focus on their choice of 1 or more of those behaviors.

After 15 months of working with a DM educator, participants lowered their A1C levels by 67%, on average, and their LDL cholesterol levels by 53%. After receiving DM education, 25% of patients had high blood pressure, compared with 32% before the study. The A1C test measures the concentration of glucose (sugar) in the blood, a reflection of how well the diabetes is being controlled. There was a 7% increase in patients achieving an A1C level lower than 7% over the course of the study.

 “Our patient-centered approach prioritizes our patients’ needs,” said Lovelyamma Varghese, MS, FNP, BC, RN, and Director of Nursing Practice and quality for the Ambulatory Care Network at New York-Presbyterian Hospital, New York. “As diabetes educators, we partner with providers, fellow dietitians and nurses, community health workers and most importantly, patients. We can go into their homes, speak their language, identify opportunities for behavioral changes, even open the fridge and see what’s in there-it’s a partnership.”

The patients worked with DM educators as part of their care through a holistic patient-centered medical home approach, including coordination of care between providers and culturally competent communication.

Diabetes Education Enhances Health and Quality of Life

Mindfulness training helped US veterans who had diabetes mellitus (DM) significantly lower their DM-related distress and blood sugar levels and improve their DM self-management, according to early research. The intervention included focused breathing and awareness training.

The research was to be presented today at AADE14, the 

American Association of Diabetes Educators Annual Meeting & Exhibition

The researchers analyzed whether including mindfulness training as part of veterans’ DM self-management education helps them cope with DM-related distress. Their study included 28 veterans with types 1 and 2 DM who participated in the Mind-STRIDE (Mindful Stress Reduction In Diabetes Education) program at VA Pittsburgh. The program presented information on what stress does to the body and how mindfulness training can help reduce stress and provided practical training in mindful stress-reduction techniques. The participants learned how to do the following:

• Separate thoughts, emotions, and body sensations.

The participants were directed to practice the techniques of focused breathing and mindful movement for 15 minutes every day for 3 months. They were given a CD to guide them through the exercises at home.

Monica M. DiNardo, PhD and colleagues used scientifically validated questionnaires to measure DM-related distress and DM self-management behaviors; the veterans completed them before the class, 1 month after the class, and 3 months later. During those times, researchers also conducted A1C tests before the class and then at 3 months to measure the 3-month average concentration of glucose.

After 3 months, on average, the veterans’ DM-related distress decreased by 41%. Their A1C levels dropped significantly, from 8.3 to 7.3. Their DM management improved-they were meeting more AADE-7™ self-care behavioral goals: (1) healthy eating, (2) being active, (3) monitoring, (4) taking medication, (5) problem solving, (6) healthy coping, and (7) reducing risks.

“We were surprised at the dramatic decrease in diabetes-related stress,” said Dr DiNardo, who is the principal investigator, diabetes educator, nurse practitioner, and health scientist at the VA Pittsburgh Healthcare System. “The veterans said the more mindful they were, the better they were able to manage their diabetes.”

More than 25% of the 1 million US veterans who have received care through the Veterans Administration have DM, it was noted, and many patients with DM experience DM-related distress, resulting in poorer self-management and adverse effects of the disease.

Early research shows that this kind of program decreases distress and lowers blood sugar levels.