Type 2 Diabetes ICYMI

Key clinical point: Patients with first-ever stroke and type 2 diabetes mellitus (T2D) who receive metformin treatment (MT) show lower stroke severity, case fatality, and disability rates.

Major finding: MT vs non-MT group had a lower rate of in-hospital case fatality (odds ratio [OR] 0.63; 95% CI 0.47-0.84), 12-month case fatality (OR 0.69; 95% CI 0.50-0.88), and 12-month disability (OR 0.83; 95% CI 0.70-0.95).

Study details: The data come from a prospective, hospital-based cohort study including 7587 patients with first-ever stroke and T2D, of which 3593 (47.36%) received MT (MT group) and 3994 (52.64%) did not receive MT (non-MT group).

Disclosures: This study was supported by the National Major Public Health Service Projects, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Natural Science Foundation of Tianjin, and China Postdoctoral Science Foundation, among others. The authors declared no conflicts of interest.

Source: Tu WJ et al. Metformin use is associated with low risk of case fatality and disability rates in first-ever stroke patients with type 2 diabetes. Ther Adv Chronic Dis. 2022 (Apr 19). Doi: 10.1177/20406223221076894

Key clinical point: Patients with first-ever stroke and type 2 diabetes mellitus (T2D) who receive metformin treatment (MT) show lower stroke severity, case fatality, and disability rates.

Major finding: MT vs non-MT group had a lower rate of in-hospital case fatality (odds ratio [OR] 0.63; 95% CI 0.47-0.84), 12-month case fatality (OR 0.69; 95% CI 0.50-0.88), and 12-month disability (OR 0.83; 95% CI 0.70-0.95).

Study details: The data come from a prospective, hospital-based cohort study including 7587 patients with first-ever stroke and T2D, of which 3593 (47.36%) received MT (MT group) and 3994 (52.64%) did not receive MT (non-MT group).

Disclosures: This study was supported by the National Major Public Health Service Projects, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Natural Science Foundation of Tianjin, and China Postdoctoral Science Foundation, among others. The authors declared no conflicts of interest.

Source: Tu WJ et al. Metformin use is associated with low risk of case fatality and disability rates in first-ever stroke patients with type 2 diabetes. Ther Adv Chronic Dis. 2022 (Apr 19). Doi: 10.1177/20406223221076894

Key clinical point: Patients with first-ever stroke and type 2 diabetes mellitus (T2D) who receive metformin treatment (MT) show lower stroke severity, case fatality, and disability rates.

Major finding: MT vs non-MT group had a lower rate of in-hospital case fatality (odds ratio [OR] 0.63; 95% CI 0.47-0.84), 12-month case fatality (OR 0.69; 95% CI 0.50-0.88), and 12-month disability (OR 0.83; 95% CI 0.70-0.95).

Study details: The data come from a prospective, hospital-based cohort study including 7587 patients with first-ever stroke and T2D, of which 3593 (47.36%) received MT (MT group) and 3994 (52.64%) did not receive MT (non-MT group).

Disclosures: This study was supported by the National Major Public Health Service Projects, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Natural Science Foundation of Tianjin, and China Postdoctoral Science Foundation, among others. The authors declared no conflicts of interest.

Source: Tu WJ et al. Metformin use is associated with low risk of case fatality and disability rates in first-ever stroke patients with type 2 diabetes. Ther Adv Chronic Dis. 2022 (Apr 19). Doi: 10.1177/20406223221076894

Key clinical point: Body weight gain and loss are significantly associated with a higher risk for hip fracture in patients with type 2 diabetes (T2D), irrespective of the body mass index.

Major finding: Compared with stable weight, body weight loss of ≥10% (adjusted hazard ratio [aHR] 1.605; 95% CI 1.493-1.725) and 5%-10% (aHR 1.237; 95% CI 1.177-1.300) and gain of ≥10% (aHR 1.457; 95% CI 1.318-1.612) and 5%-≤10% (aHR 1.234; 95% CI 1.156-1.318) were associated with a higher risk for hip fracture.

Study details: Findings are from a nationwide cohort study including 1,447,579 patients aged >40 years with T2D who reported 11,848 hip fracture events.

Disclosures: The study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Lee SW et al. Weight change and the risk of hip fractures in patients with type 2 diabetes: A nationwide cohort study. Osteoporos Int. 2022 (Apr 19). Doi: 10.1007/s00198-022-06398-8

Key clinical point: Body weight gain and loss are significantly associated with a higher risk for hip fracture in patients with type 2 diabetes (T2D), irrespective of the body mass index.

Major finding: Compared with stable weight, body weight loss of ≥10% (adjusted hazard ratio [aHR] 1.605; 95% CI 1.493-1.725) and 5%-10% (aHR 1.237; 95% CI 1.177-1.300) and gain of ≥10% (aHR 1.457; 95% CI 1.318-1.612) and 5%-≤10% (aHR 1.234; 95% CI 1.156-1.318) were associated with a higher risk for hip fracture.

Study details: Findings are from a nationwide cohort study including 1,447,579 patients aged >40 years with T2D who reported 11,848 hip fracture events.

Disclosures: The study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Lee SW et al. Weight change and the risk of hip fractures in patients with type 2 diabetes: A nationwide cohort study. Osteoporos Int. 2022 (Apr 19). Doi: 10.1007/s00198-022-06398-8

Key clinical point: Body weight gain and loss are significantly associated with a higher risk for hip fracture in patients with type 2 diabetes (T2D), irrespective of the body mass index.

Major finding: Compared with stable weight, body weight loss of ≥10% (adjusted hazard ratio [aHR] 1.605; 95% CI 1.493-1.725) and 5%-10% (aHR 1.237; 95% CI 1.177-1.300) and gain of ≥10% (aHR 1.457; 95% CI 1.318-1.612) and 5%-≤10% (aHR 1.234; 95% CI 1.156-1.318) were associated with a higher risk for hip fracture.

Study details: Findings are from a nationwide cohort study including 1,447,579 patients aged >40 years with T2D who reported 11,848 hip fracture events.

Disclosures: The study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declared no conflicts of interest.

Source: Lee SW et al. Weight change and the risk of hip fractures in patients with type 2 diabetes: A nationwide cohort study. Osteoporos Int. 2022 (Apr 19). Doi: 10.1007/s00198-022-06398-8

Key clinical point: Treatment intensification with quadruple therapy showed similar glucose lowering efficacy as once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus (T2D). However, low C-peptide levels reduced the therapeutic efficacy of GLP-1RA therapy but not quadruple therapy.

Major finding: At 24 weeks, both quadruple and GLP-1RA-based triple therapies significantly reduced glycated hemoglobin level (both therapies: mean reduction −1.1%; P < .001); however, the glucose-lowering effects of GLP-1RA vs quadruple therapy were weaker in patients with low C-peptide levels (mean −0.1% vs −1.3%; P = .04).

Study details: Findings are from a real-world study including 96 patients with poorly controlled T2D refractory to triple oral therapy who underwent treatment intensification with quadruple oral therapy (n = 50) or once-weekly GLP-1RA-based triple therapy (n = 46).

Disclosures: The study received no specific funding. The authors declared no conflicts of interest.

Source: Kim M et al. the efficacy of treatment intensification by quadruple oral therapy compared to GLP-1RA therapy in poorly controlled type 2 diabetes mellitus patients: A real-world data study. Diabetes Metab J. 2022 (Apr 29). Doi: 10.4093/dmj.2021.0373

Key clinical point: Treatment intensification with quadruple therapy showed similar glucose lowering efficacy as once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus (T2D). However, low C-peptide levels reduced the therapeutic efficacy of GLP-1RA therapy but not quadruple therapy.

Major finding: At 24 weeks, both quadruple and GLP-1RA-based triple therapies significantly reduced glycated hemoglobin level (both therapies: mean reduction −1.1%; P < .001); however, the glucose-lowering effects of GLP-1RA vs quadruple therapy were weaker in patients with low C-peptide levels (mean −0.1% vs −1.3%; P = .04).

Study details: Findings are from a real-world study including 96 patients with poorly controlled T2D refractory to triple oral therapy who underwent treatment intensification with quadruple oral therapy (n = 50) or once-weekly GLP-1RA-based triple therapy (n = 46).

Disclosures: The study received no specific funding. The authors declared no conflicts of interest.

Source: Kim M et al. the efficacy of treatment intensification by quadruple oral therapy compared to GLP-1RA therapy in poorly controlled type 2 diabetes mellitus patients: A real-world data study. Diabetes Metab J. 2022 (Apr 29). Doi: 10.4093/dmj.2021.0373

Key clinical point: Treatment intensification with quadruple therapy showed similar glucose lowering efficacy as once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus (T2D). However, low C-peptide levels reduced the therapeutic efficacy of GLP-1RA therapy but not quadruple therapy.

Major finding: At 24 weeks, both quadruple and GLP-1RA-based triple therapies significantly reduced glycated hemoglobin level (both therapies: mean reduction −1.1%; P < .001); however, the glucose-lowering effects of GLP-1RA vs quadruple therapy were weaker in patients with low C-peptide levels (mean −0.1% vs −1.3%; P = .04).

Study details: Findings are from a real-world study including 96 patients with poorly controlled T2D refractory to triple oral therapy who underwent treatment intensification with quadruple oral therapy (n = 50) or once-weekly GLP-1RA-based triple therapy (n = 46).

Disclosures: The study received no specific funding. The authors declared no conflicts of interest.

Source: Kim M et al. the efficacy of treatment intensification by quadruple oral therapy compared to GLP-1RA therapy in poorly controlled type 2 diabetes mellitus patients: A real-world data study. Diabetes Metab J. 2022 (Apr 29). Doi: 10.4093/dmj.2021.0373

Key clinical point: Prolonged treatment with proton pump inhibitors (PPI) is associated with a higher risk for type 2 diabetes (T2D), thus unnecessary prescription, particularly for long-term use, should be avoided.

Major finding: The risk for T2D was higher among patients receiving PPI for 8 weeks to 6 months (odds ratio [OR] 1.19; 95% CI 1.15-1.24), 6 months to 2 years (OR 1.43; 95% CI 1.38-1.49), and >2 years (OR 1.56; 95% CI 1.49-1.64) than those receiving PPI for <8 weeks (P_trend < .001), particularly among younger patients and those with worse clinical complexity.

Study details: Findings are from a nested case-control study including 777,420 patients aged ≥40 years who received PPI, of which 50,535 were diagnosed with T2D and matched with control participants.

Disclosures: The study was funded by the Italian Ministry of Education, University, and Research. G Corrao declared being an advisory board member, receiving research support, and participating in numerous projects funded by various sources.

Source: Ciardullo S et al. Prolonged use of proton pump inhibitors and risk of type 2 diabetes: Results from a large population-based nested case-control study. J Clin Endocrinol Metab. 2022 (Apr 16). Doi: 10.1210/clinem/dgac231

Key clinical point: Prolonged treatment with proton pump inhibitors (PPI) is associated with a higher risk for type 2 diabetes (T2D), thus unnecessary prescription, particularly for long-term use, should be avoided.

Major finding: The risk for T2D was higher among patients receiving PPI for 8 weeks to 6 months (odds ratio [OR] 1.19; 95% CI 1.15-1.24), 6 months to 2 years (OR 1.43; 95% CI 1.38-1.49), and >2 years (OR 1.56; 95% CI 1.49-1.64) than those receiving PPI for <8 weeks (P_trend < .001), particularly among younger patients and those with worse clinical complexity.

Study details: Findings are from a nested case-control study including 777,420 patients aged ≥40 years who received PPI, of which 50,535 were diagnosed with T2D and matched with control participants.

Disclosures: The study was funded by the Italian Ministry of Education, University, and Research. G Corrao declared being an advisory board member, receiving research support, and participating in numerous projects funded by various sources.

Source: Ciardullo S et al. Prolonged use of proton pump inhibitors and risk of type 2 diabetes: Results from a large population-based nested case-control study. J Clin Endocrinol Metab. 2022 (Apr 16). Doi: 10.1210/clinem/dgac231

Key clinical point: Prolonged treatment with proton pump inhibitors (PPI) is associated with a higher risk for type 2 diabetes (T2D), thus unnecessary prescription, particularly for long-term use, should be avoided.

Major finding: The risk for T2D was higher among patients receiving PPI for 8 weeks to 6 months (odds ratio [OR] 1.19; 95% CI 1.15-1.24), 6 months to 2 years (OR 1.43; 95% CI 1.38-1.49), and >2 years (OR 1.56; 95% CI 1.49-1.64) than those receiving PPI for <8 weeks (P_trend < .001), particularly among younger patients and those with worse clinical complexity.

Study details: Findings are from a nested case-control study including 777,420 patients aged ≥40 years who received PPI, of which 50,535 were diagnosed with T2D and matched with control participants.

Disclosures: The study was funded by the Italian Ministry of Education, University, and Research. G Corrao declared being an advisory board member, receiving research support, and participating in numerous projects funded by various sources.

Source: Ciardullo S et al. Prolonged use of proton pump inhibitors and risk of type 2 diabetes: Results from a large population-based nested case-control study. J Clin Endocrinol Metab. 2022 (Apr 16). Doi: 10.1210/clinem/dgac231

Key clinical point: Treatment intensification with 300 units/mL insulin glargine (Gla-300) in patients with type 2 diabetes mellitus (T2D) receiving glucagon-like peptide-1 receptor agonists (GLP-1 RA) significantly improved glycemic control without increasing the risk for hypoglycemia.

Major finding: Addition of Gla-300 to GLP-1 RA therapy significantly reduced glycated hemoglobin (HbA1c) level (mean change −0.97% ± 1.6%; P < .0001) and significantly increased the proportion of patients achieving glycemic control (HbA1c <7.0%: change 17.34%; HbA1c <8.0%: change 31.73%; both P < .001), with no significant changes in overall incidence or event rate of hypoglycemia.

Study details: The data come from a retrospective analysis of 271 insulin-naive patients with T2D receiving GLP-1 RA who underwent treatment intensification with Gla-300.

Disclosures: This study was funded by Sanofi. TS Bailey declared receiving research support and consulting and speaking honoraria from various sources, including Sanofi. C Nicholls, J Gill, and J Westerbacka declared being employees and stockholders of Sanofi.

Source: Bailey TS et al. Real-world outcomes of addition of insulin glargine 300 U/mL (Gla-300) to GLP-1 RA therapy in people with type 2 diabetes: The DELIVER-G study. Diabetes Obes Metab. 2022 (May 1). Doi: 10.1111/dom.14739

Key clinical point: Treatment intensification with 300 units/mL insulin glargine (Gla-300) in patients with type 2 diabetes mellitus (T2D) receiving glucagon-like peptide-1 receptor agonists (GLP-1 RA) significantly improved glycemic control without increasing the risk for hypoglycemia.

Major finding: Addition of Gla-300 to GLP-1 RA therapy significantly reduced glycated hemoglobin (HbA1c) level (mean change −0.97% ± 1.6%; P < .0001) and significantly increased the proportion of patients achieving glycemic control (HbA1c <7.0%: change 17.34%; HbA1c <8.0%: change 31.73%; both P < .001), with no significant changes in overall incidence or event rate of hypoglycemia.

Study details: The data come from a retrospective analysis of 271 insulin-naive patients with T2D receiving GLP-1 RA who underwent treatment intensification with Gla-300.

Disclosures: This study was funded by Sanofi. TS Bailey declared receiving research support and consulting and speaking honoraria from various sources, including Sanofi. C Nicholls, J Gill, and J Westerbacka declared being employees and stockholders of Sanofi.

Source: Bailey TS et al. Real-world outcomes of addition of insulin glargine 300 U/mL (Gla-300) to GLP-1 RA therapy in people with type 2 diabetes: The DELIVER-G study. Diabetes Obes Metab. 2022 (May 1). Doi: 10.1111/dom.14739

Key clinical point: Treatment intensification with 300 units/mL insulin glargine (Gla-300) in patients with type 2 diabetes mellitus (T2D) receiving glucagon-like peptide-1 receptor agonists (GLP-1 RA) significantly improved glycemic control without increasing the risk for hypoglycemia.

Major finding: Addition of Gla-300 to GLP-1 RA therapy significantly reduced glycated hemoglobin (HbA1c) level (mean change −0.97% ± 1.6%; P < .0001) and significantly increased the proportion of patients achieving glycemic control (HbA1c <7.0%: change 17.34%; HbA1c <8.0%: change 31.73%; both P < .001), with no significant changes in overall incidence or event rate of hypoglycemia.

Study details: The data come from a retrospective analysis of 271 insulin-naive patients with T2D receiving GLP-1 RA who underwent treatment intensification with Gla-300.

Disclosures: This study was funded by Sanofi. TS Bailey declared receiving research support and consulting and speaking honoraria from various sources, including Sanofi. C Nicholls, J Gill, and J Westerbacka declared being employees and stockholders of Sanofi.

Source: Bailey TS et al. Real-world outcomes of addition of insulin glargine 300 U/mL (Gla-300) to GLP-1 RA therapy in people with type 2 diabetes: The DELIVER-G study. Diabetes Obes Metab. 2022 (May 1). Doi: 10.1111/dom.14739

Key clinical point: Severe hypoglycemia (SH) is associated with a greater risk for corrected QT (QTc) prolongation in patients with type 2 diabetes mellitus (T2D), especially in younger participants (age <61.9 years), irrespective of other risk factors.

Major finding: Patients with T2D and SH had a higher risk for QTc prolongation (adjusted risk ratio [aRR] 1.66; 95% CI 1.16-2.38), with the risk being higher in patients with 1 (aRR 1.57; 95% CI 1.04-2.39) and ≥2 (aRR 2.01; 95% CI 1.07-3.78) vs no SH episodes and the association remaining significant in younger (aRR 2.63; P = .001) but not in older (P = .170) patients.

Study details: This prospective cohort study included 8277 patients with T2D from the ACCORD study, of which 324 had ≥1 SH episodes and 517 developed QTc prolongation over a 5-year median follow-up.

Disclosures: The study received no specific funding. GC Fonarow reported being a consultant for various organizations.

Source: Kaze AD et al. Severe hypoglycemia and incidence of QT interval prolongation among adults with type 2 diabetes. J Clin Endocrinol Metab. 2022 (Apr 9). Doi: 10.1210/clinem/dgac195

Key clinical point: Severe hypoglycemia (SH) is associated with a greater risk for corrected QT (QTc) prolongation in patients with type 2 diabetes mellitus (T2D), especially in younger participants (age <61.9 years), irrespective of other risk factors.

Major finding: Patients with T2D and SH had a higher risk for QTc prolongation (adjusted risk ratio [aRR] 1.66; 95% CI 1.16-2.38), with the risk being higher in patients with 1 (aRR 1.57; 95% CI 1.04-2.39) and ≥2 (aRR 2.01; 95% CI 1.07-3.78) vs no SH episodes and the association remaining significant in younger (aRR 2.63; P = .001) but not in older (P = .170) patients.

Study details: This prospective cohort study included 8277 patients with T2D from the ACCORD study, of which 324 had ≥1 SH episodes and 517 developed QTc prolongation over a 5-year median follow-up.

Disclosures: The study received no specific funding. GC Fonarow reported being a consultant for various organizations.

Source: Kaze AD et al. Severe hypoglycemia and incidence of QT interval prolongation among adults with type 2 diabetes. J Clin Endocrinol Metab. 2022 (Apr 9). Doi: 10.1210/clinem/dgac195

Key clinical point: Severe hypoglycemia (SH) is associated with a greater risk for corrected QT (QTc) prolongation in patients with type 2 diabetes mellitus (T2D), especially in younger participants (age <61.9 years), irrespective of other risk factors.

Major finding: Patients with T2D and SH had a higher risk for QTc prolongation (adjusted risk ratio [aRR] 1.66; 95% CI 1.16-2.38), with the risk being higher in patients with 1 (aRR 1.57; 95% CI 1.04-2.39) and ≥2 (aRR 2.01; 95% CI 1.07-3.78) vs no SH episodes and the association remaining significant in younger (aRR 2.63; P = .001) but not in older (P = .170) patients.

Study details: This prospective cohort study included 8277 patients with T2D from the ACCORD study, of which 324 had ≥1 SH episodes and 517 developed QTc prolongation over a 5-year median follow-up.

Disclosures: The study received no specific funding. GC Fonarow reported being a consultant for various organizations.

Source: Kaze AD et al. Severe hypoglycemia and incidence of QT interval prolongation among adults with type 2 diabetes. J Clin Endocrinol Metab. 2022 (Apr 9). Doi: 10.1210/clinem/dgac195

Key clinical point: Once-weekly tirzepatide vs insulin degludec effectuates superior glycemic control, as measured by continuous glucose monitoring, in patients with inadequately controlled type 2 diabetes (T2D) on metformin with or without a sodium-glucose cotransporter-2 (SGLT2) inhibitor.

Major finding: At 52 weeks, patients receiving 5 mg tirzepatide (estimated treatment difference [ETD] 12%; P = .031), 10 mg (ETD 24%; P < .0001), and 15 mg (ETD 25%; P < .0001) vs insulin degludec spent significantly more time in the tight target range (blood glucose concentration 71-140 mg/dL).

Study details: This substudy of the SURPASS-3 trial included 243 insulin-naive patients with type T2D inadequately controlled on metformin with or without an SGLT2 inhibitor who were randomly assigned to receive once-weekly tirzepatide (5, 10, or 15 mg; n = 188) or insulin degludec (n = 55).

Disclosures: The study was funded by Eli Lilly and Company. Two authors reported being consultants or receiving advisory board member or speaker honoraria from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Battelino T et al. Efficacy of once-weekly tirzepatide versus once-daily insulin degludec on glycaemic control measured by continuous glucose monitoring in adults with type 2 diabetes (SURPASS-3 CGM): A substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022;10(6):407-417 (Apr 22). Doi: 10.1016/S2213-8587(22)00077-8

Key clinical point: Once-weekly tirzepatide vs insulin degludec effectuates superior glycemic control, as measured by continuous glucose monitoring, in patients with inadequately controlled type 2 diabetes (T2D) on metformin with or without a sodium-glucose cotransporter-2 (SGLT2) inhibitor.

Major finding: At 52 weeks, patients receiving 5 mg tirzepatide (estimated treatment difference [ETD] 12%; P = .031), 10 mg (ETD 24%; P < .0001), and 15 mg (ETD 25%; P < .0001) vs insulin degludec spent significantly more time in the tight target range (blood glucose concentration 71-140 mg/dL).

Study details: This substudy of the SURPASS-3 trial included 243 insulin-naive patients with type T2D inadequately controlled on metformin with or without an SGLT2 inhibitor who were randomly assigned to receive once-weekly tirzepatide (5, 10, or 15 mg; n = 188) or insulin degludec (n = 55).

Disclosures: The study was funded by Eli Lilly and Company. Two authors reported being consultants or receiving advisory board member or speaker honoraria from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Battelino T et al. Efficacy of once-weekly tirzepatide versus once-daily insulin degludec on glycaemic control measured by continuous glucose monitoring in adults with type 2 diabetes (SURPASS-3 CGM): A substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022;10(6):407-417 (Apr 22). Doi: 10.1016/S2213-8587(22)00077-8

Key clinical point: Once-weekly tirzepatide vs insulin degludec effectuates superior glycemic control, as measured by continuous glucose monitoring, in patients with inadequately controlled type 2 diabetes (T2D) on metformin with or without a sodium-glucose cotransporter-2 (SGLT2) inhibitor.

Major finding: At 52 weeks, patients receiving 5 mg tirzepatide (estimated treatment difference [ETD] 12%; P = .031), 10 mg (ETD 24%; P < .0001), and 15 mg (ETD 25%; P < .0001) vs insulin degludec spent significantly more time in the tight target range (blood glucose concentration 71-140 mg/dL).

Study details: This substudy of the SURPASS-3 trial included 243 insulin-naive patients with type T2D inadequately controlled on metformin with or without an SGLT2 inhibitor who were randomly assigned to receive once-weekly tirzepatide (5, 10, or 15 mg; n = 188) or insulin degludec (n = 55).

Disclosures: The study was funded by Eli Lilly and Company. Two authors reported being consultants or receiving advisory board member or speaker honoraria from various sources, including Eli Lilly. The other authors are employees and shareholders of Eli Lilly.

Source: Battelino T et al. Efficacy of once-weekly tirzepatide versus once-daily insulin degludec on glycaemic control measured by continuous glucose monitoring in adults with type 2 diabetes (SURPASS-3 CGM): A substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022;10(6):407-417 (Apr 22). Doi: 10.1016/S2213-8587(22)00077-8

Tirzepatide (Mounjaro) – the new twincretin approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes – was priced by Lilly, the company that will market the drug, at a list price of $974.33 for four weekly doses regardless of dose size, a cost that adds up to about $12,666 per year, according to a statement made on May 20 by a Lilly spokesperson.

This price puts tirzepatide, which combines the activity of two of the primary human incretins in one molecule, roughly in the same ballpark as what might be its main competitor, semaglutide (Ozempic) for type 2 diabetes, which retails at many U.S. pharmacies for about $925 for four weekly doses, or about $12,025 per year, although Ozempic’s posted retail price is about $100 higher for four doses.

According to the Lilly spokesperson, discount programs could reduce the monthly out-of-pocket cost for patients to as little as $25.

Tirzepatide, which received approval from the FDA on May 13, is a dual glucagonlike peptide–1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, which is indicated as Wegovy for weight loss in patients with obesity regardless of diabetes status.

A version of this article first appeared on Medscape.com.

Tirzepatide (Mounjaro) – the new twincretin approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes – was priced by Lilly, the company that will market the drug, at a list price of $974.33 for four weekly doses regardless of dose size, a cost that adds up to about $12,666 per year, according to a statement made on May 20 by a Lilly spokesperson.

This price puts tirzepatide, which combines the activity of two of the primary human incretins in one molecule, roughly in the same ballpark as what might be its main competitor, semaglutide (Ozempic) for type 2 diabetes, which retails at many U.S. pharmacies for about $925 for four weekly doses, or about $12,025 per year, although Ozempic’s posted retail price is about $100 higher for four doses.

According to the Lilly spokesperson, discount programs could reduce the monthly out-of-pocket cost for patients to as little as $25.

Tirzepatide, which received approval from the FDA on May 13, is a dual glucagonlike peptide–1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, which is indicated as Wegovy for weight loss in patients with obesity regardless of diabetes status.

A version of this article first appeared on Medscape.com.

Tirzepatide (Mounjaro) – the new twincretin approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes – was priced by Lilly, the company that will market the drug, at a list price of $974.33 for four weekly doses regardless of dose size, a cost that adds up to about $12,666 per year, according to a statement made on May 20 by a Lilly spokesperson.

This price puts tirzepatide, which combines the activity of two of the primary human incretins in one molecule, roughly in the same ballpark as what might be its main competitor, semaglutide (Ozempic) for type 2 diabetes, which retails at many U.S. pharmacies for about $925 for four weekly doses, or about $12,025 per year, although Ozempic’s posted retail price is about $100 higher for four doses.

According to the Lilly spokesperson, discount programs could reduce the monthly out-of-pocket cost for patients to as little as $25.

Tirzepatide, which received approval from the FDA on May 13, is a dual glucagonlike peptide–1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide agonist. Several GLP-1 receptor agonists are already approved in the United States, including semaglutide, which is indicated as Wegovy for weight loss in patients with obesity regardless of diabetes status.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Does having had a COVID-19 infection increase your risk for the development of diabetes subsequently? Some data say yes and other data say no. No matter what, it’s obviously important to screen people for diabetes routinely, pandemic or not. Remember, screening should start at age 35.

For over a decade, we have known that SARS-type viruses bind to beta cells. This could cause either direct damage to the beta cell or in some way trigger beta cell autoimmunity. We also know that COVID-19 infection increases the levels of inflammatory mediators, which could cause damage to beta cells and potentially to insulin receptors. There is a potential that having had a COVID-19 infection could increase rates of developing type 1 and/or type 2 diabetes.

However, there are other possible causes for people to develop diabetes after having a COVID-19 infection. A COVID-19 infection could cause one to seek medical care, unmasking latent type 1 and/or type 2 diabetes by causing infection-related insulin resistance and worsening preexisting mild hypoglycemia. In addition, people could have sought more medical care in the years since the pandemic has been ebbing, which may make it look like cases have increased.

For example, during the worst of the pandemic, I had multiple referrals for “COVID-19–caused new-onset diabetes” only to find that the patient had an A1c level above 10% and a history of mildly elevated blood glucose levels. This suggests to me that COVID-19 did not cause the diabetes per se but rather worsened an underlying glucose abnormality.

Since the pandemic has improved, I have also seen people diagnosed with type 2 diabetes that I think is associated with pandemic-related weight gain and inactivity.

The bigger issue is what is happening to people after COVID-19 infection who lack risk factors. What about those who we didn’t think were at high risk to get diabetes to begin with and didn’t have prediabetes?

An article by Xie and Al-Aly in The Lancet Diabetes & Endocrinology showed an increase in rates of diabetes in a large VA cohort among those who had a COVID-19 infection compared with both a contemporaneous control who did not have COVID-19 and a historical control. The researchers looked at the patient data 1 year after they’d had COVID-19, so it wasn’t the immediate post–COVID-19 phase but several months later.

They found that the risk for incident type 2 diabetes development was increased by 40% after adjusting for many risk factors. This included individuals who didn’t have traditional risk factors before they developed type 2 diabetes.

What does this mean clinically? First, pandemic or not, people need screening for diabetes and encouragement to have a healthy lifestyle. There may be an increased risk for the diagnosis of type 2 diabetes after COVID-19 infection due to a variety of different mechanisms.

As for people with type 1 diabetes, we also don’t know if having a COVID-19 infection increases their risk. We do know that there was an increase in the severity of diabetic ketoacidosis presentation during the pandemic, so we need to be sure that we reinforce sick-day rules with our patients with type 1 diabetes and that all individuals with type 1 diabetes have the ability to test their ketone levels at home.

In people with new-onset diabetes, whether type 1 or type 2, caused by COVID-19 or not, we need to treat appropriately based on their clinical situation.

Data from registries started during the pandemic will provide more definitive answers and help us find out if there is a relationship between having had COVID-19 infection and developing diabetes.

Perhaps that can help us better understand the mechanisms behind the development of diabetes overall.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Does having had a COVID-19 infection increase your risk for the development of diabetes subsequently? Some data say yes and other data say no. No matter what, it’s obviously important to screen people for diabetes routinely, pandemic or not. Remember, screening should start at age 35.

For over a decade, we have known that SARS-type viruses bind to beta cells. This could cause either direct damage to the beta cell or in some way trigger beta cell autoimmunity. We also know that COVID-19 infection increases the levels of inflammatory mediators, which could cause damage to beta cells and potentially to insulin receptors. There is a potential that having had a COVID-19 infection could increase rates of developing type 1 and/or type 2 diabetes.

However, there are other possible causes for people to develop diabetes after having a COVID-19 infection. A COVID-19 infection could cause one to seek medical care, unmasking latent type 1 and/or type 2 diabetes by causing infection-related insulin resistance and worsening preexisting mild hypoglycemia. In addition, people could have sought more medical care in the years since the pandemic has been ebbing, which may make it look like cases have increased.

For example, during the worst of the pandemic, I had multiple referrals for “COVID-19–caused new-onset diabetes” only to find that the patient had an A1c level above 10% and a history of mildly elevated blood glucose levels. This suggests to me that COVID-19 did not cause the diabetes per se but rather worsened an underlying glucose abnormality.

Since the pandemic has improved, I have also seen people diagnosed with type 2 diabetes that I think is associated with pandemic-related weight gain and inactivity.

The bigger issue is what is happening to people after COVID-19 infection who lack risk factors. What about those who we didn’t think were at high risk to get diabetes to begin with and didn’t have prediabetes?

An article by Xie and Al-Aly in The Lancet Diabetes & Endocrinology showed an increase in rates of diabetes in a large VA cohort among those who had a COVID-19 infection compared with both a contemporaneous control who did not have COVID-19 and a historical control. The researchers looked at the patient data 1 year after they’d had COVID-19, so it wasn’t the immediate post–COVID-19 phase but several months later.

They found that the risk for incident type 2 diabetes development was increased by 40% after adjusting for many risk factors. This included individuals who didn’t have traditional risk factors before they developed type 2 diabetes.

What does this mean clinically? First, pandemic or not, people need screening for diabetes and encouragement to have a healthy lifestyle. There may be an increased risk for the diagnosis of type 2 diabetes after COVID-19 infection due to a variety of different mechanisms.

As for people with type 1 diabetes, we also don’t know if having a COVID-19 infection increases their risk. We do know that there was an increase in the severity of diabetic ketoacidosis presentation during the pandemic, so we need to be sure that we reinforce sick-day rules with our patients with type 1 diabetes and that all individuals with type 1 diabetes have the ability to test their ketone levels at home.

In people with new-onset diabetes, whether type 1 or type 2, caused by COVID-19 or not, we need to treat appropriately based on their clinical situation.

Data from registries started during the pandemic will provide more definitive answers and help us find out if there is a relationship between having had COVID-19 infection and developing diabetes.

Perhaps that can help us better understand the mechanisms behind the development of diabetes overall.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Does having had a COVID-19 infection increase your risk for the development of diabetes subsequently? Some data say yes and other data say no. No matter what, it’s obviously important to screen people for diabetes routinely, pandemic or not. Remember, screening should start at age 35.

For over a decade, we have known that SARS-type viruses bind to beta cells. This could cause either direct damage to the beta cell or in some way trigger beta cell autoimmunity. We also know that COVID-19 infection increases the levels of inflammatory mediators, which could cause damage to beta cells and potentially to insulin receptors. There is a potential that having had a COVID-19 infection could increase rates of developing type 1 and/or type 2 diabetes.

However, there are other possible causes for people to develop diabetes after having a COVID-19 infection. A COVID-19 infection could cause one to seek medical care, unmasking latent type 1 and/or type 2 diabetes by causing infection-related insulin resistance and worsening preexisting mild hypoglycemia. In addition, people could have sought more medical care in the years since the pandemic has been ebbing, which may make it look like cases have increased.

For example, during the worst of the pandemic, I had multiple referrals for “COVID-19–caused new-onset diabetes” only to find that the patient had an A1c level above 10% and a history of mildly elevated blood glucose levels. This suggests to me that COVID-19 did not cause the diabetes per se but rather worsened an underlying glucose abnormality.

Since the pandemic has improved, I have also seen people diagnosed with type 2 diabetes that I think is associated with pandemic-related weight gain and inactivity.

The bigger issue is what is happening to people after COVID-19 infection who lack risk factors. What about those who we didn’t think were at high risk to get diabetes to begin with and didn’t have prediabetes?

An article by Xie and Al-Aly in The Lancet Diabetes & Endocrinology showed an increase in rates of diabetes in a large VA cohort among those who had a COVID-19 infection compared with both a contemporaneous control who did not have COVID-19 and a historical control. The researchers looked at the patient data 1 year after they’d had COVID-19, so it wasn’t the immediate post–COVID-19 phase but several months later.

They found that the risk for incident type 2 diabetes development was increased by 40% after adjusting for many risk factors. This included individuals who didn’t have traditional risk factors before they developed type 2 diabetes.

What does this mean clinically? First, pandemic or not, people need screening for diabetes and encouragement to have a healthy lifestyle. There may be an increased risk for the diagnosis of type 2 diabetes after COVID-19 infection due to a variety of different mechanisms.

As for people with type 1 diabetes, we also don’t know if having a COVID-19 infection increases their risk. We do know that there was an increase in the severity of diabetic ketoacidosis presentation during the pandemic, so we need to be sure that we reinforce sick-day rules with our patients with type 1 diabetes and that all individuals with type 1 diabetes have the ability to test their ketone levels at home.

In people with new-onset diabetes, whether type 1 or type 2, caused by COVID-19 or not, we need to treat appropriately based on their clinical situation.

Data from registries started during the pandemic will provide more definitive answers and help us find out if there is a relationship between having had COVID-19 infection and developing diabetes.

Perhaps that can help us better understand the mechanisms behind the development of diabetes overall.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She disclosed ties with Abbott Diabetes Care, AstraZeneca, Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article first appeared on Medscape.com.

Davida F. Kruger, MSN, APN-BC, BC-ADM
Ms. Kruger has been a certified nurse practitioner in diabetes at Henry Ford Health System in Detroit, MI, for more than 35 years. Ms. Kruger has been a co-investigator on numerous studies of diabetes interventions and care, including the National Institutes of Health–funded multicenter EDIC and ACCORD trials.

She is a past Chair of the American Diabetes Association (ADA) Research Foundation and has served on the ADA Research Policy Committee. She is also an ADA Past President (Health Care and Education). She has also served as editor-in-chief of 2 American Diabetes Association (ADA) journals, Diabetes Spectrum and Clinical Diabetes.

Our diabetes clinic in Detroit is ground zero for diabetes care and education.

High-risk obstetrician gynecologists, cardiologists, nephrologists, and primary care providers, which are all specialties seeing more patients with type 2 diabetes (T2D) comorbidities, are coming to us or sharing patient cases to learn more about diabetes care, newer medications, and the technology needed to help disease management. Considering the complexity of the disease, its comorbidities, the long list of medications, and the human skills required to help these individuals, our clinic has long considered that patients are better served by a team of providers with experience in the intricacies and nuances of this chronic disease.

With over 40 years in the trenches, I can write without equivocation that the treatment of patients with diabetes requires a team approach involving diabetes educators, nurse practitioners, physician assistants, pharmacists, physicians, and nutritionists, who have long known that diabetes is a serious, deadly disease. 

Some facts to prove my point: 
When I started treating people with  diabetes, 4% of the US population had the disease. Life expectancy was about 74 years. Today, 11% of the population has diabetes, and life expectancy is closer to 78 years. Longer life, for someone with diabetes, means more time with kidney disease, cardiovascular problems, neuropathy, macular degeneration, and more.T2D is no longer just an adult disease. We are treating T2D in a much younger population. The Centers for Disease Control and Prevention says from 2002 to 2015, the incidence rate for people <20 years rose 4.8% per year. 
In 2019, the World Health Organization said that 16,300 people < 25 years old died from diabetes, and most of these deaths were from type 1 diabetes.
If we maintain the status quo, between now and 2050, 33% of the adult population in this country could have this disease. 
Our clinic has enrolled  at least 3500 patients with some type of diabetes. 

The list of therapies ─ and more importantly the different classes of therapies ─ has grown significantly since the time when sulfonylureas, metformin, and insulin were the only therapies available. Today, there are at least 9 classes of medications to treat type 2 diabetes. 

Considering that patients with T2D, most of whom are overweight or obese, also have heart disease, kidney disease, and more, the collective input from various kinds of healthcare providers to discuss how these medications can work together, or not, is beyond beneficial. The literature shows that a multidisciplinary team improves patient outcomes in the T2D population. The literature also shows that despite therapeutic advances, most of these patients have disease that is not well controlled, for a variety of reasons.

Patients and Attitudes
I was riding in an elevator with a rheumatologist a few years ago. He told me that my patients were all “fat” and “responsible for their situation.” I told him an elevator ride could not cover the amount of education he needed, so I invited him to call me. There are many reasons why people develop T2D and carrying too much weight is a significant one. We tell our patients that this extra weight puts stress on the natural production of insulin. The result is that less organic insulin is produced so more manufactured insulin is prescribed, and this puts weight on the patient. 

Patients have busy lives, and those with diabetes are no different; their lives get in the way of managing their disease. Some need to remember to take 3 or 4 injections a day. They forget an injection at lunch because their routine has been disrupted; they forget at bedtime because they fell asleep on the sofa. Or they had to feed their children dinner quickly to make it to a teacher’s meeting, so they forgot their medication. But it is vital that they maintain their insulin injection schedule. Research says missing 2.1 meal-related injections a week increases glycated hemoglobin (A1c) by 0.3% to 0.4%.

Most people with T2D will eventually need insulin. For someone with diabetes – and for their family members – hypoglycemia is a real fear. Hypoglycemia has significant physical (eg, irregular heartbeat, shakiness) and mental (eg, anxiety, irritability) effects. In response, patients can treat themselves with glucose tablets or simple carbohydrates (between 15 and 30 g). If the patient is unconscious, the family may need to use injectable glucagon. This is where the benefits of a continuous glucose monitor come in.
Patients can see the hypoglycemic state they are approaching so they can treat a low blood glucose level on their own before others need to. 

Our clinic members focus on having open, honest conversations with our patients about how their lives affect their diabetes. We encourage them to choose a nutrition plan or see our dietitian. Some do phenomenally well with plans like Weight Watchers, but others do not. Whatever they choose, our dietitians aim to help them stay on it, with weekly check-ins, teleconferences, and appointments.

Communication goes both ways. Our patients tell us constantly that they do not want another medication. Diabetes is an expensive disease, and most of our patients take at least 5 medications, prescribed by nephrologists, cardiologists, endocrinologists, and family physicians. Our clinical pharmacists and other team members try to find ways to bring those costs down; sometimes we cannot.

Some Pointers
It is not a bad idea to keep a flowchart on your phone that details which diabetes drug is applicable under which circumstances, and when it is not applicable. While most are complementary, a list would detail how each of the new medications work, how they work together and how they benefit patients.

Some wisdom learned in the trenches: 

• Do not shy away from starting a newly diagnosed patient on metformin and a second agent. The American Diabetes Association guidelines say that more intensive initial treatment can be beneficial. If the patient’s  A1c is elevated, consider using 2 medications upon diagnosis. 
• Using a sulfonylurea, which stimulates insulin secretion, as a second-line therapy alone can increase risk of myocardial infarction, all-cause mortality, and severe hypoglycemia (hazard ratios, 1.26, 1.28, and 7.60, respectively); these medications also cause weight gain. The sulfonylureas put pressure on the beta cells to work harder. More importantly, we do not know what these medications do to the cardiovascular system in the long term.
• If the patient has cardiovascular disease, then, in combination with metformin, use a glucagon-like peptide 1 receptor agonist (GLP-1) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If the patient has kidney disease, start with an SGLT2 inhibitor. And yes, you can prescribe both at the same time. 
• SGLT2 inhibitors lower glucose levels by preventing the kidneys from reabsorbing glucose. The GLP-1 agonists encourage insulin production and inhibit glucagon secretion  after meals. Neither of these medications are known to add weight; they are linked with weight loss. 
• If your patient is on a dipeptidyl peptidase 4 (DPP-4) inhibitor and is moving to a GLP-1 receptor agonist, stop the DDP-4 before starting the GLP-1 since both target the incretin system to control blood glucose levels.

While years in the making, new medications and technologies now available for T2D have given healthcare providers more options for their patients, and patients have better opportunities to achieve their treatment goals. 
 

Davida F. Kruger, MSN, APN-BC, BC-ADM
Ms. Kruger has been a certified nurse practitioner in diabetes at Henry Ford Health System in Detroit, MI, for more than 35 years. Ms. Kruger has been a co-investigator on numerous studies of diabetes interventions and care, including the National Institutes of Health–funded multicenter EDIC and ACCORD trials.

She is a past Chair of the American Diabetes Association (ADA) Research Foundation and has served on the ADA Research Policy Committee. She is also an ADA Past President (Health Care and Education). She has also served as editor-in-chief of 2 American Diabetes Association (ADA) journals, Diabetes Spectrum and Clinical Diabetes.

Our diabetes clinic in Detroit is ground zero for diabetes care and education.

High-risk obstetrician gynecologists, cardiologists, nephrologists, and primary care providers, which are all specialties seeing more patients with type 2 diabetes (T2D) comorbidities, are coming to us or sharing patient cases to learn more about diabetes care, newer medications, and the technology needed to help disease management. Considering the complexity of the disease, its comorbidities, the long list of medications, and the human skills required to help these individuals, our clinic has long considered that patients are better served by a team of providers with experience in the intricacies and nuances of this chronic disease.

With over 40 years in the trenches, I can write without equivocation that the treatment of patients with diabetes requires a team approach involving diabetes educators, nurse practitioners, physician assistants, pharmacists, physicians, and nutritionists, who have long known that diabetes is a serious, deadly disease. 

Some facts to prove my point: 
When I started treating people with  diabetes, 4% of the US population had the disease. Life expectancy was about 74 years. Today, 11% of the population has diabetes, and life expectancy is closer to 78 years. Longer life, for someone with diabetes, means more time with kidney disease, cardiovascular problems, neuropathy, macular degeneration, and more.T2D is no longer just an adult disease. We are treating T2D in a much younger population. The Centers for Disease Control and Prevention says from 2002 to 2015, the incidence rate for people <20 years rose 4.8% per year. 
In 2019, the World Health Organization said that 16,300 people < 25 years old died from diabetes, and most of these deaths were from type 1 diabetes.
If we maintain the status quo, between now and 2050, 33% of the adult population in this country could have this disease. 
Our clinic has enrolled  at least 3500 patients with some type of diabetes. 

The list of therapies ─ and more importantly the different classes of therapies ─ has grown significantly since the time when sulfonylureas, metformin, and insulin were the only therapies available. Today, there are at least 9 classes of medications to treat type 2 diabetes. 

Considering that patients with T2D, most of whom are overweight or obese, also have heart disease, kidney disease, and more, the collective input from various kinds of healthcare providers to discuss how these medications can work together, or not, is beyond beneficial. The literature shows that a multidisciplinary team improves patient outcomes in the T2D population. The literature also shows that despite therapeutic advances, most of these patients have disease that is not well controlled, for a variety of reasons.

Patients and Attitudes
I was riding in an elevator with a rheumatologist a few years ago. He told me that my patients were all “fat” and “responsible for their situation.” I told him an elevator ride could not cover the amount of education he needed, so I invited him to call me. There are many reasons why people develop T2D and carrying too much weight is a significant one. We tell our patients that this extra weight puts stress on the natural production of insulin. The result is that less organic insulin is produced so more manufactured insulin is prescribed, and this puts weight on the patient. 

Patients have busy lives, and those with diabetes are no different; their lives get in the way of managing their disease. Some need to remember to take 3 or 4 injections a day. They forget an injection at lunch because their routine has been disrupted; they forget at bedtime because they fell asleep on the sofa. Or they had to feed their children dinner quickly to make it to a teacher’s meeting, so they forgot their medication. But it is vital that they maintain their insulin injection schedule. Research says missing 2.1 meal-related injections a week increases glycated hemoglobin (A1c) by 0.3% to 0.4%.

Most people with T2D will eventually need insulin. For someone with diabetes – and for their family members – hypoglycemia is a real fear. Hypoglycemia has significant physical (eg, irregular heartbeat, shakiness) and mental (eg, anxiety, irritability) effects. In response, patients can treat themselves with glucose tablets or simple carbohydrates (between 15 and 30 g). If the patient is unconscious, the family may need to use injectable glucagon. This is where the benefits of a continuous glucose monitor come in.
Patients can see the hypoglycemic state they are approaching so they can treat a low blood glucose level on their own before others need to. 

Our clinic members focus on having open, honest conversations with our patients about how their lives affect their diabetes. We encourage them to choose a nutrition plan or see our dietitian. Some do phenomenally well with plans like Weight Watchers, but others do not. Whatever they choose, our dietitians aim to help them stay on it, with weekly check-ins, teleconferences, and appointments.

Communication goes both ways. Our patients tell us constantly that they do not want another medication. Diabetes is an expensive disease, and most of our patients take at least 5 medications, prescribed by nephrologists, cardiologists, endocrinologists, and family physicians. Our clinical pharmacists and other team members try to find ways to bring those costs down; sometimes we cannot.

Some Pointers
It is not a bad idea to keep a flowchart on your phone that details which diabetes drug is applicable under which circumstances, and when it is not applicable. While most are complementary, a list would detail how each of the new medications work, how they work together and how they benefit patients.

Some wisdom learned in the trenches: 

• Do not shy away from starting a newly diagnosed patient on metformin and a second agent. The American Diabetes Association guidelines say that more intensive initial treatment can be beneficial. If the patient’s  A1c is elevated, consider using 2 medications upon diagnosis. 
• Using a sulfonylurea, which stimulates insulin secretion, as a second-line therapy alone can increase risk of myocardial infarction, all-cause mortality, and severe hypoglycemia (hazard ratios, 1.26, 1.28, and 7.60, respectively); these medications also cause weight gain. The sulfonylureas put pressure on the beta cells to work harder. More importantly, we do not know what these medications do to the cardiovascular system in the long term.
• If the patient has cardiovascular disease, then, in combination with metformin, use a glucagon-like peptide 1 receptor agonist (GLP-1) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If the patient has kidney disease, start with an SGLT2 inhibitor. And yes, you can prescribe both at the same time. 
• SGLT2 inhibitors lower glucose levels by preventing the kidneys from reabsorbing glucose. The GLP-1 agonists encourage insulin production and inhibit glucagon secretion  after meals. Neither of these medications are known to add weight; they are linked with weight loss. 
• If your patient is on a dipeptidyl peptidase 4 (DPP-4) inhibitor and is moving to a GLP-1 receptor agonist, stop the DDP-4 before starting the GLP-1 since both target the incretin system to control blood glucose levels.

While years in the making, new medications and technologies now available for T2D have given healthcare providers more options for their patients, and patients have better opportunities to achieve their treatment goals. 
 

Davida F. Kruger, MSN, APN-BC, BC-ADM
Ms. Kruger has been a certified nurse practitioner in diabetes at Henry Ford Health System in Detroit, MI, for more than 35 years. Ms. Kruger has been a co-investigator on numerous studies of diabetes interventions and care, including the National Institutes of Health–funded multicenter EDIC and ACCORD trials.

She is a past Chair of the American Diabetes Association (ADA) Research Foundation and has served on the ADA Research Policy Committee. She is also an ADA Past President (Health Care and Education). She has also served as editor-in-chief of 2 American Diabetes Association (ADA) journals, Diabetes Spectrum and Clinical Diabetes.

Our diabetes clinic in Detroit is ground zero for diabetes care and education.

High-risk obstetrician gynecologists, cardiologists, nephrologists, and primary care providers, which are all specialties seeing more patients with type 2 diabetes (T2D) comorbidities, are coming to us or sharing patient cases to learn more about diabetes care, newer medications, and the technology needed to help disease management. Considering the complexity of the disease, its comorbidities, the long list of medications, and the human skills required to help these individuals, our clinic has long considered that patients are better served by a team of providers with experience in the intricacies and nuances of this chronic disease.

With over 40 years in the trenches, I can write without equivocation that the treatment of patients with diabetes requires a team approach involving diabetes educators, nurse practitioners, physician assistants, pharmacists, physicians, and nutritionists, who have long known that diabetes is a serious, deadly disease. 

Some facts to prove my point: 
When I started treating people with  diabetes, 4% of the US population had the disease. Life expectancy was about 74 years. Today, 11% of the population has diabetes, and life expectancy is closer to 78 years. Longer life, for someone with diabetes, means more time with kidney disease, cardiovascular problems, neuropathy, macular degeneration, and more.T2D is no longer just an adult disease. We are treating T2D in a much younger population. The Centers for Disease Control and Prevention says from 2002 to 2015, the incidence rate for people <20 years rose 4.8% per year. 
In 2019, the World Health Organization said that 16,300 people < 25 years old died from diabetes, and most of these deaths were from type 1 diabetes.
If we maintain the status quo, between now and 2050, 33% of the adult population in this country could have this disease. 
Our clinic has enrolled  at least 3500 patients with some type of diabetes. 

The list of therapies ─ and more importantly the different classes of therapies ─ has grown significantly since the time when sulfonylureas, metformin, and insulin were the only therapies available. Today, there are at least 9 classes of medications to treat type 2 diabetes. 

Considering that patients with T2D, most of whom are overweight or obese, also have heart disease, kidney disease, and more, the collective input from various kinds of healthcare providers to discuss how these medications can work together, or not, is beyond beneficial. The literature shows that a multidisciplinary team improves patient outcomes in the T2D population. The literature also shows that despite therapeutic advances, most of these patients have disease that is not well controlled, for a variety of reasons.

Patients and Attitudes
I was riding in an elevator with a rheumatologist a few years ago. He told me that my patients were all “fat” and “responsible for their situation.” I told him an elevator ride could not cover the amount of education he needed, so I invited him to call me. There are many reasons why people develop T2D and carrying too much weight is a significant one. We tell our patients that this extra weight puts stress on the natural production of insulin. The result is that less organic insulin is produced so more manufactured insulin is prescribed, and this puts weight on the patient. 

Patients have busy lives, and those with diabetes are no different; their lives get in the way of managing their disease. Some need to remember to take 3 or 4 injections a day. They forget an injection at lunch because their routine has been disrupted; they forget at bedtime because they fell asleep on the sofa. Or they had to feed their children dinner quickly to make it to a teacher’s meeting, so they forgot their medication. But it is vital that they maintain their insulin injection schedule. Research says missing 2.1 meal-related injections a week increases glycated hemoglobin (A1c) by 0.3% to 0.4%.

Most people with T2D will eventually need insulin. For someone with diabetes – and for their family members – hypoglycemia is a real fear. Hypoglycemia has significant physical (eg, irregular heartbeat, shakiness) and mental (eg, anxiety, irritability) effects. In response, patients can treat themselves with glucose tablets or simple carbohydrates (between 15 and 30 g). If the patient is unconscious, the family may need to use injectable glucagon. This is where the benefits of a continuous glucose monitor come in.
Patients can see the hypoglycemic state they are approaching so they can treat a low blood glucose level on their own before others need to. 

Our clinic members focus on having open, honest conversations with our patients about how their lives affect their diabetes. We encourage them to choose a nutrition plan or see our dietitian. Some do phenomenally well with plans like Weight Watchers, but others do not. Whatever they choose, our dietitians aim to help them stay on it, with weekly check-ins, teleconferences, and appointments.

Communication goes both ways. Our patients tell us constantly that they do not want another medication. Diabetes is an expensive disease, and most of our patients take at least 5 medications, prescribed by nephrologists, cardiologists, endocrinologists, and family physicians. Our clinical pharmacists and other team members try to find ways to bring those costs down; sometimes we cannot.

Some Pointers
It is not a bad idea to keep a flowchart on your phone that details which diabetes drug is applicable under which circumstances, and when it is not applicable. While most are complementary, a list would detail how each of the new medications work, how they work together and how they benefit patients.

Some wisdom learned in the trenches: 

• Do not shy away from starting a newly diagnosed patient on metformin and a second agent. The American Diabetes Association guidelines say that more intensive initial treatment can be beneficial. If the patient’s  A1c is elevated, consider using 2 medications upon diagnosis. 
• Using a sulfonylurea, which stimulates insulin secretion, as a second-line therapy alone can increase risk of myocardial infarction, all-cause mortality, and severe hypoglycemia (hazard ratios, 1.26, 1.28, and 7.60, respectively); these medications also cause weight gain. The sulfonylureas put pressure on the beta cells to work harder. More importantly, we do not know what these medications do to the cardiovascular system in the long term.
• If the patient has cardiovascular disease, then, in combination with metformin, use a glucagon-like peptide 1 receptor agonist (GLP-1) or a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If the patient has kidney disease, start with an SGLT2 inhibitor. And yes, you can prescribe both at the same time. 
• SGLT2 inhibitors lower glucose levels by preventing the kidneys from reabsorbing glucose. The GLP-1 agonists encourage insulin production and inhibit glucagon secretion  after meals. Neither of these medications are known to add weight; they are linked with weight loss. 
• If your patient is on a dipeptidyl peptidase 4 (DPP-4) inhibitor and is moving to a GLP-1 receptor agonist, stop the DDP-4 before starting the GLP-1 since both target the incretin system to control blood glucose levels.

While years in the making, new medications and technologies now available for T2D have given healthcare providers more options for their patients, and patients have better opportunities to achieve their treatment goals.