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Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.

The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.

Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
 

New Drugs

The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).

Recommendations

The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.

SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.

Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.

Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.

Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.

The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).

Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
 

 

 

Considerations for Practice

Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.

The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.

The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.

The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

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Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.

The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.

Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
 

New Drugs

The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).

Recommendations

The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.

SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.

Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.

Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.

Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.

The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).

Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
 

 

 

Considerations for Practice

Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.

The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.

The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.

The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Type 2 diabetes (T2D) is the most common form of diabetes, representing more than 90% of all cases worldwide. The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.

The main therapeutic goals for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the 2017 guidelines of the American College of Physicians.

Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.
 

New Drugs

The pharmacologic treatments that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).

Recommendations

The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.

SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.

Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in specific warnings. Both classes of drugs lead to weight loss.

Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.

Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.

The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).

Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.
 

 

 

Considerations for Practice

Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.

The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.

The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.

The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

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The prevalence of T2D is increasing globally, mainly because of behavioral and social factors related to obesity, diet, and physical activity. The International Diabetes Federation estimated in <span class="Hyperlink"><a href="https://www.ncbi.nlm.nih.gov/books/NBK581934/">its 2021 report</a></span> that 537 million adults aged between 20 and 79 years have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million by 2030 and 743 million by 2045.</p> <p>The <span class="Hyperlink"><a href="https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0728-6">main therapeutic goals</a></span> for patients with T2D include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which represent nearly half of all deaths among adults with T2D. Despite the multiple treatment options available, 16% of adults with T2D have inadequate glycemic control, including hemoglobin A1c levels greater than 9%, even though glycemic control was the focus of the <span class="Hyperlink"><a href="https://www.acpjournals.org/doi/full/10.7326/M16-1860?rfr_dat=cr_pub++0pubmed&amp;url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org">2017 guidelines</a></span> of the American College of Physicians.<br/><br/>Therefore, the ACP deemed it necessary to update the previous guidelines, considering new evidence on the efficacy and harms of new pharmacologic treatments in adults with T2D with the goal of reducing the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in these patients.<br/><br/></p> <h2>New Drugs</h2> <p>The <span class="Hyperlink"><a href="https://www.acpjournals.org/doi/full/10.7326/M23-2788?rfr_dat=cr_pub++0pubmed&amp;url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org">pharmacologic treatments</a></span> that the ACP considered while updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (that is, dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist and a glucose-dependent insulinotropic polypeptide receptor agonist (that is, tirzepatide), sodium-glucose cotransporter 2 (SGLT-2) inhibitors (that is, canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (that is, alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (that is, insulin glargine and insulin degludec).</p> <h2>Recommendations</h2> <p>The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), CKD progression, and hospitalization resulting from heart failure, according to the document. Use a GLP-1 agonist to reduce the risk for all-cause mortality, MACE, and strokes.</p> <p>SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality than placebo or usual care. In indirect comparison, SGLT-2 inhibitors probably reduce the risk for hospitalization resulting from heart failure, while GLP-1 agonists probably reduce the risk for strokes.<br/><br/>Neither class of drugs causes severe hypoglycemia, but both are associated with various harms, as reported in <span class="Hyperlink"><a href="https://www.acpjournals.org/doi/full/10.7326/M23-1492?rfr_dat=cr_pub++0pubmed&amp;url_ver=Z39.88-2003&amp;rfr_id=ori%3Arid%3Acrossref.org">specific warnings</a></span>. Both classes of drugs lead to weight loss.<br/><br/>Compared with long-acting insulins, SGLT-2 inhibitors can reduce, and GLP-1 agonists probably reduce, all-cause mortality. Compared with DPP-4 inhibitors, GLP-1 agonists probably reduce all-cause mortality.<br/><br/>Compared with DPP-4 inhibitors, SGLT-2 inhibitors probably reduce MACE, as well as compared with sulfonylureas.<br/><br/>The ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with inadequately controlled T2D to reduce morbidity and all-cause mortality (strong recommendation, high certainty of evidence).<br/><br/>Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), CKD progression, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization caused by CHF and probably increase the risk for MACE and CKD progression. Compared with GLP-1 agonists, they probably increase all-cause mortality and hospitalization caused by CHF and the risk for MACE. Metformin is the most common usual therapy in the studies considered.<br/><br/></p> <h2>Considerations for Practice</h2> <p>Metformin (unless contraindicated) and lifestyle modifications represent the first step in managing T2D in most patients, according to the ACP.</p> <p>The choice of additional therapy requires a risk/benefit assessment and should be personalized on the basis of patient preferences, glycemic control goals, comorbidities, and the risk for hypoglycemia. SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD, according to the ACP. GLP-1 agonists can be added in patients with T2D at increased risk for stroke or for whom total body weight loss is a significant therapeutic goal.<br/><br/>The A1c target should be considered between 7% and 8% in most adults with T2D, and de-escalation of pharmacologic treatments should be considered for A1c levels less than 6.5%. Self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist, according to the ACP.<br/><br/>The document also holds that, in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or stopped due to the increased risk for severe hypoglycemia.</p> <p> <em>This story was translated from <span class="Hyperlink"><a href="https://www.univadis.it/viewarticle/diabete-mellito-tipo-2-e-nuovi-trattamenti-2024a1000ad3">Univadis Italy</a></span>, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. 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