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CME / ABIM MOC / CE

Consensus Panel Algorithm for Type 2 Diabetes Treatment

  • Authors: News Author: Miriam E. Tucker; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 7/29/2020
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 7/29/2021
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Target Audience and Goal Statement

This article is intended for primary care clinicians, diabetologists/endocrinologists/metabolic medicine clinicians, cardiologists, family medicine clinicians, internists, nurses, pharmacists, and other members of the health care team who treat and manage patients with type 2 diabetes.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.

Upon completion of this activity, participants will be able to:

  • Assess 3 basic recommendations regarding choice of medications for the treatment of type 2 diabetes, based on an expert opinion from a European Consensus Panel
  • Evaluate additional considerations regarding use of sulfonylureas for the treatment of type 2 diabetes, based on an expert opinion from a European Consensus Panel
  • Outline implications for the healthcare team


Disclosures

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Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


News Author

  • Miriam E. Tucker

    Freelance writer, Medscape

    Disclosures

    Disclosure: Miriam E. Tucker has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor/Nurse Planner

  • Hazel Dennison, DNP, RN, FNP, CPHQ, CNE

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Disclosure: Hazel Dennison, DNP, RN, FNP, CPHQ, CNE, has disclosed no relevant financial relationships.

CME Reviewer

  • Esther Nyarko, PharmD

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

Medscape, LLC staff have disclosed that they have no relevant financial relationships. 


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CME / ABIM MOC / CE

Consensus Panel Algorithm for Type 2 Diabetes Treatment

Authors: News Author: Miriam E. Tucker; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME / ABIM MOC / CE Released: 7/29/2020

Valid for credit through: 7/29/2021

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Clinical Context

Given the large number of drugs available for the treatment of type 2 diabetes, choosing the optimal regimen for any given patient requires careful consideration. Sulfonylureas and metformin are some of the most widely prescribed agents in the world. However, continued use of sulfonylureas is controversial in light of the various advantages of newer agents.

Although clinicians should follow published treatment guidelines and recommendations in their general approach to diabetes management, expert opinions may foster better understanding of local practices and better decision-making for individual patients. The goal of a report of consensus opinions was to offer additional guidance on sulfonylurea use in type 2 diabetes, as well as options among 12 different classes of pharmacological agents currently available for type 2 diabetes treatment.

Study Synopsis and Perspective

A European consensus statement advises limiting routine use of sulfonylureas for the treatment of type 2 diabetes to "settings that are resource-constrained and in the short term."

The writing project, organized by medical communications agency Edra and supported by AstraZeneca, was published online June 1 in Diabetes Obesity and Metabolism.

The authors point to current guidelines to "govern the general approach to diabetes management" and offer this new consensus paper as supplemental guidance specifically on the use of sulfonylureas as second-line treatment (after metformin) in type 2 diabetes.

The statement was prompted by "the large differences among guidelines from different countries in sulfonylureas positioning in type 2 diabetes treatment algorithms," say lead author Agostino Consoli, MD, professor of endocrinology at the D'Annunzio University of Chieti-Pescara, Chieti, Italy, and colleagues,

"[G]uidelines and approaches are changing rapidly and most agree that preference should be given to agents whose benefits extend beyond glucose-lowering," write Dr Consoli and coauthors, who are from several other European countries as well as Israel and Canada.

"Notwithstanding, [sulfonylureas] and metformin remain the most widely prescribed anti-hyperglycemic agents worldwide."

Three Basic Recommendations:

The article summarizes evidence supporting use of newer classes of glucose-lowering agents and discusses the hypoglycemia and weight gain risks associated with sulfonylureas. It then provides 3 basic recommendations in the conclusion section, as follows.

First, because the main goal of type 2 diabetes treatment is to reduce cardiorenal endpoints and prolong survival, newer diabetes medications including sodium-glucose cotransporter type 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and to a lesser extent, dipeptidyl peptidase-4 (DPP-4) inhibitors are preferred over sulfonylureas as second-line treatments after metformin. This is based on evidence of the minimal hypoglycemic risk associated with their use, their positive (GLP-1 agonists, SGLT2 inhibitors) or neutral (DPP-4 inhibitors) cardiovascular effects, their positive renal effects (SGLT2 inhibitors >> GLP-1 agonists > DPP-4 inhibitors), their neutral (DPP-4 inhibitors) or positive (GLP-1 agonists, SGLT2 inhibitors) effects on body weight, their possible longer glycemic durability, and their ease of use, mostly without titration or need for self-blood glucose monitoring.

Second, although newer diabetes medications may be preferred in all patients with type 2 diabetes for whom they are not contraindicated, SGLT2 inhibitors and/or GLP-1 agonists are particularly strongly recommended for people with established cardiovascular disease or who are at very high risk in the absence of contraindications. (No study has shown a cardiovascular or renal benefit for sulfonylureas.)

Finally, routine use of sulfonylureas as second-line agents might be acceptable in settings that are resource-constrained and in the short term. When they are prescribed, the following should be considered: gliclazide may be the preferred agent (because of its relatively lower hypoglycemia risk), patients should be educated about hypoglycemia, use of self-monitoring of blood glucose should be considered to minimize hypoglycemic adverse effects, and "Given the accrued evidence of the positive impact of SGLT2 inhibitors and GLP-1 agonists on vascular, cardiac, and renal endpoints, use of sulfonylureas instead of SGLT2 inhibitors and GLP-1 agonists needs a strong and well-supported motivation, since it may deprive the patient of possibly important cardiorenal protective effects," the panel concludes.

The project was sponsored by Edra, a medical communications agency, with unconditional funding provided by AstraZeneca. Dr Consoli has reported consulting relationships with AstraZeneca and Novo Nordisk; participating in advisory panels for Abbot, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Takeda; receiving speaker fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bruno Farmaceutici, Eli Lilly, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Takeda; and receiving research supporting from AstraZeneca, Eli Lilly, and Novo Nordisk.

Diabetes Obes Metab. Published online June 1, 2020.

Study Highlights

  • This expert opinion from a European Consensus Panel summarized current local treatment guidelines in European countries, which vary widely among countries regarding sulfonylurea use in type 2 diabetes.
  • Sulfonylureas are often suggested as second-line treatment after metformin and are often ranked equally with newer glucose-lowering medications.
  • Advantages of sodium-glucose cotransporter type 2 inhibitors and glucagon-like peptide-1 receptor agonists, based on strong evidence, include low hypoglycemia risk, enhanced weight loss, and a positive effect on vascular, cardiac, and renal endpoints.
  • Using sulfonylurea instead of SGLT2 inhibitors and GLP-1 receptor agonists may therefore deprive patients of these benefits, including potentially important cardiorenal effects.
  • For patients with known cardiovascular disease or who are at very high cardiovascular risk, diabetes management should include use of SGLT2 inhibitors and/or GLP-1 receptor agonists in the absence of contraindications.
  • In resource-constrained settings, however, routine use of sulfonylureas as second-line agents is still acceptable.
  • On the basis of the available evidence, the experts made 3 recommendations regarding sulfonylurea use.
  • Because the leading priority in type 2 diabetes treatment is to improve overall outcomes, including cardiovascular and renal events and survival, newer diabetes medications should be preferred over sulfonylureas as second-line glucose-lowering medications.
  • These preferred medications are SGLT2 inhibitors, GLP-1 receptor agonists, and to a lesser extent, DPP-4 inhibitors.
  • Rationale for this recommendation includes the minimal hypoglycemic risk associated with their use, their positive (GLP-1 receptor agonists, SGLT2 inhibitors) or neutral (DPP-4 inhibitors) cardiovascular effects, their positive renal effects (SGLT2 inhibitors >> GLP-1 receptor agonists > DPP-4 inhibitors), their neutral (DPP-4 inhibitors) or positive (GLP-1 receptor agonists, SGLT2 inhibitors) effects on body weight, possibly longer glycemic durability, and ease of use, with less need for titration and self-monitoring of blood glucose.
  • Newer diabetes agents might be preferable in all patients with type 2 diabetes and without specific contraindications to their use.
  • In patients with known cardiovascular disease or who are at very high cardiovascular risk, SGLT2 inhibitors and/or GLP-1 receptor agonists should be used as part of the diabetes treatment regimen unless there are contraindications.
  • Use of sulfonylureas is not known to be associated with increased cardiovascular risk, but there is no evidence for improved cardiovascular and renal risk in patients with type 2 diabetes treated with sulfonylureas.
  • As per the American Diabetes Association Standards of Care, routine use of sulfonylureas as second-line agents might be acceptable in resource-constrained settings and in the short term.
  • When sulfonylureas are prescribed, gliclazide may be the preferred agent and clinicians should consider patient education on hypoglycemia and self-monitoring of blood glucose.
  • Given the body of evidence regarding the benefits of SGLT2 inhibitors and GLP-1 receptor agonists on vascular, cardiac, and renal endpoints, use of sulfonylureas instead of SGLT2 inhibitors and GLP-1 receptor agonists needs a strong and well-supported motivation, as it may deprive the patient of possibly important cardiorenal protection.
  • In terms of specific recommendations for sulfonylurea use, the experts suggested sulfonylurea monotherapy only when metformin, SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and pioglitazone are contraindicated, not tolerated, unavailable, or not affordable.
  • When these 4 newer agents are suitable, sulfonylureas should be considered the last option among second-line drugs, even as a part of dual combination therapy, because of the risk for hypoglycemia and weight gain, less durability, need for titrations, and self-monitoring of blood glucose in some countries.
  • To intensify dual therapy, clinicians may consider sulfonylureas in triple-combination therapy when needed to improve HbA1c, primarily to achieve microvascular protection, but newer agents are preferred when suitable.
  • Adding sulfonylurea to metformin plus SGLT2 inhibitors plus GLP-1 receptor agonists, or to metformin plus DPP-4 inhibitors plus SGLT2 inhibitors, might help lower HbA1c for purposes of microvascular protection.
  • Sulfonylureas should not be used in patients who use insulin, especially in those receiving intensified insulin regimens, because of the multiplicative risk for hypoglycemia and the absence of a dedicated trial showing additional benefit.
  • Sulfonylureas should be used with extreme caution in the elderly because of higher risk for prolonged, severe hypoglycemia; less concern regarding microvascular risk; and lack of protection from cardiovascular events by glucose control with sulfonylureas.
  • Sulfonylureas should be used with great caution in patients with chronic kidney disease because of overexposure and greater risk for hypoglycemia, but they are not contraindicated in patients with cardiovascular disease.
  • If hypoglycemia is detected during sulfonylurea treatment, the sulfonylurea should be discontinued or titrated down.
  • Many drug-related factors govern the choice of glucose-lowering medications: effects on blood glucose, body weight, cardiovascular and renal outcomes; risk for hypoglycemia; renal clearance; durability of the blood glucose lowering effect; mechanism of action, such as need for residual beta cell function; ease of use, with need for titration and/or self-monitoring of blood glucose; and adverse effects.
  • Clinicians should balance these factors and patient preferences against costs while considering local regulations governing reimbursement and international guidelines, all of which change rapidly and vary among different countries, regions, and specialist groups.
  • Cost considerations should include not only the acquisition costs of glucose-lowering medications but also the direct and indirect costs related to acute and chronic complications, such as dialysis, foot disease, and cardiac complications.
  • Although sulfonylureas are inexpensive and effectively lower blood glucose, their use is associated with hypoglycemia and weight gain.
  • Hypoglycemia is associated with poorer quality of life, increased risk for falls and coma, loss of confidence in treatment, increased healthcare costs, and loss of working days.

Clinical Implications

  • Because the leading priority in type 2 diabetes treatment is to improve overall outcomes, including cardiovascular and renal events and survival, newer diabetes medications should be preferred over sulfonylureas as second-line glucose-lowering medications.
  • Clinicians should balance drug-related factors and patient preferences against costs, including not only the acquisition costs of glucose-lowering medications but also the direct and indirect costs related to acute and chronic complications, such as dialysis, foot disease, and cardiac complications.
  • Implications for the Healthcare Team: The leading priority in type 2 diabetes treatment is to improve overall outcomes, including cardiovascular and renal events and survival. Incorporating newer diabetes medications, such as SGLT2 inhibitors, CLP-1 receptor agonists or DPP-4 inhibitors into treatment regimens should be considered over sulfonylureas as second-line glucose-lowering medications. Advantages of SGLT2 inhibitors and GLP-1 receptor agonists, based on strong evidence, are low hypoglycemia risk, enhanced weight loss, and positive effect on vascular, cardiac, and renal endpoints.

 

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