My approach to working with patients
Much of my work over the past 3 decades as a practicing endocrinologist has centered on helping my patients with diabetes take greater control of their blood sugar. This is one of the reasons I founded the nonprofit organization Taking Control of Your Diabetes and authored a book of the same name. In working with these patients, I try to tailor my advice in the form of tangible and practical actions.
Of course, medication may play a large part in a patient’s path. So beyond the vital task of educating patients, it’s my role as a clinician to stay on top of the research and treatment options as they become available. I want to give my patients choices that are appropriate for their needs as they take a more active part in their care. This includes when it’s time for them to add basal insulin to their treatment regimen.
Steven Edelman, MD
- Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California, San Diego and the Veterans Affairs Healthcare System of San Diego
- Founder, Director, and Chairman of the Board of the nonprofit organization Taking Control of Your Diabetes
- Author of 18 books and 200+ published articles
- 2013 U.S. World Report: Top 1% of US Endocrinologists
- 10-time winner of the San Diego Magazine Top Doctors in San Diego Award
What do I consider when prescribing a basal insulin?
A1C reductions1
FPG reductions1
Flat and stable profile1-3
Risk of hypoglycemia
When it’s time for my patients to start taking basal insulin, I consider a number of factors when deciding which to prescribe. First and foremost, I look for an insulin that provides A1C and FPG reductions and has been proven to help patients reach their blood sugar goals. I also look for a flat and stable profile, and of course safety plays a role in the decision as well. That’s why I often prescribe Tresiba® to my adult patients with diabetes.
“Before prescribing insulin, I turn to clinical study results to review efficacy and safety.”
Steven Edelman, MD
Examining the efficacy and safety of Tresiba® FlexTouch® U-200 vs insulin glargine U-100 in insulin-naïve adult patients with type 2 diabetes1
BEGIN: Low Volume study
Duration:
26 weeks
Trial type:
treat-to-target noninferiority
Study design:
randomized, controlled, multinational, and open-label
Participants:
457 insulin-naïve adults
Primary endpoint: Change in A1C from baseline at Week 261
Secondary endpoint: Change in FPG from baseline at Week 261
When deciding which basal insulin therapy to prescribe, the first thing I do is look at the clinical data. The BEGIN: Low Volume study was a 26-week, treat-to-target, noninferiority trial that compared glycemic control of once-daily Tresiba® U-200 with insulin glargine U-100 in combination with metformin +/- DPP-4i.4 The study was randomized, controlled, multinational, and open-label. A total of 457 insulin-naïve adults participated, with 228 taking Tresiba® and 229 taking insulin glargine U-100.1,4
In this trial, Tresiba® U-200 and insulin glargine U-100 produced similar A1C reductions.
A1C reductions observed in BEGIN: Low Volume1
In this trial, Tresiba® U-200 and insulin glargine U-100 produced similar A1C reductions. Mean A1C decreased by 1.18% in the Tresiba® group and 1.22% in the insulin glargine U-100 group. After 26 weeks, adults in the Tresiba® group had a mean A1C of 7.0%, while adults in the insulin glargine U-100 group reached a mean A1C of 6.9%.1,a At Week 26, the difference in A1C reduction from baseline between Tresiba® and insulin glargine U-100 was 0.04% with a 95% CI (-0.11% to 0.19%) and met the prespecified noninferiority margin (0.4%).1
As a secondary endpoint, Tresiba® U-200 resulted in FPG reductions after 26 weeks of treatment.1
FPG reductions observed in BEGIN: Low Volume1
As for a secondary endpoint of FPG, Tresiba® U-200 resulted in FPG reductions after 26 weeks of treatment.1 Mean FPG reduction for the Tresiba® group was -71.1 mg/dL, with a mean end-of-trial FPG of 106 mg/dL. For the insulin glargine U-100 group, mean FPG reduction was -63.5 mg/dL after 26 weeks, and mean FPG was 113 mg/dL.1,b
Rates of hypoglycemia observed in BEGIN: Low Volume1
The incidence rates of hypoglycemia for patients taking Tresiba® in all type 2 diabetes trials ranged from 0% to 4.5% for severe hypoglycemiac and 28.5% to 80.9% for Novo Nordisk–defined hypoglycemiad (Tresiba® ± oral antidiabetic drugs or a basal-bolus regimen).
aBaseline: Tresiba®, 8.3%; insulin glargine U-100, 8.2%.1
bBaseline: Tresiba®, 172 mg/dL; insulin glargine U-100, 174 mg/dL.
cSevere hypoglycemia: an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
dNovo Nordisk–defined hypoglycemia: a severe hypoglycemia event or an event where laboratory or self-measured glucose calibrated to plasma was <56 mg/dL or where whole blood glucose was <50 mg/dL (ie, with or without the presence of hypoglycemic symptoms).
Results:
A1C reductions
Primary endpoint
Tresiba® was noninferior to insulin glargine U-100 in reducing A1C.1
FPG reductions
Secondary endpoint
Tresiba® U-200 resulted in FPG reductions after 26 weeks of treatment.1
See the efficacy and safety of Tresiba® in patients with type 1 diabetes.
PRIMARY CARE PERSPECTIVE
Dr Stephen Brunton on the Tresiba® duration of action
INSULIN PENS AND PRIMARY CARE
Dr Stephen Brunton’s take on prescribing Tresiba® FlexTouch®
Important Safety Information for Tresiba®
Contraindications
- Tresiba® is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to insulin degludec or any of the excipients in Tresiba®
Warnings and Precautions
- Never Share a Tresiba® FlexTouch® Pen, Needle, or Syringe Between Patients, even if the needle is changed. Patients using Tresiba® vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin, including Tresiba®. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) or who experience recurrent hypoglycemia. The long-acting effect of Tresiba® may delay recovery from hypoglycemia compared to shorter-acting insulins.
Risk Factors for Hypoglycemia: The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of Tresiba® may vary among different patients or at different times in the same patients and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to concomitant drugs. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. - Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products have been reported. To avoid medication errors between Tresiba® and other insulins, always instruct patients to always check the insulin label before each injection. To avoid dosing errors and potential overdose, never use a syringe to remove Tresiba® from the Tresiba® FlexTouch® disposable insulin prefilled pen.
- Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including Tresiba®. If hypersensitivity reactions occur, discontinue Tresiba®; treat per standard of care and monitor until symptoms and signs resolve.
- Hypokalemia: All insulins, including Tresiba®, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including Tresiba®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.
Adverse Reactions
- Adverse reactions commonly associated with Tresiba® are hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema, and weight gain.
Drug Interactions
- There are certain drugs that may cause clinically significant drug interactions with Tresiba®.
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine
Please click here for Tresiba® Prescribing Information.
Important Safety Information for Tresiba®
Contraindications
- Tresiba® is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to insulin degludec or any of the excipients in Tresiba®
Warnings and Precautions
- Never Share a Tresiba® FlexTouch® Pen, Needle, or Syringe Between Patients, even if the needle is changed. Patients using Tresiba® vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin, including Tresiba®. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) or who experience recurrent hypoglycemia. The long-acting effect of Tresiba® may delay recovery from hypoglycemia compared to shorter-acting insulins.
Risk Factors for Hypoglycemia: The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of Tresiba® may vary among different patients or at different times in the same patients and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to concomitant drugs. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. - Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products have been reported. To avoid medication errors between Tresiba® and other insulins, always instruct patients to always check the insulin label before each injection. To avoid dosing errors and potential overdose, never use a syringe to remove Tresiba® from the Tresiba® FlexTouch® disposable insulin prefilled pen.
- Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including Tresiba®. If hypersensitivity reactions occur, discontinue Tresiba®; treat per standard of care and monitor until symptoms and signs resolve.
- Hypokalemia: All insulins, including Tresiba®, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including Tresiba®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.
Adverse Reactions
- Adverse reactions commonly associated with Tresiba® are hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema, and weight gain.
Drug Interactions
- There are certain drugs that may cause clinically significant drug interactions with Tresiba®.
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine
Please click here for Tresiba® Prescribing Information.
References:
- Tresiba [package insert]. Plainsboro, NJ: Novo Nordisk Inc; July 2022.
- Heise T, Korsatko S, Nosek L, et al. J Diabetes. 2016;8(1):132-138.
- Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Diabetes Obes Metab. 2012;14(9):859-864.
- Gough SCL, Bhargava A, Jain R, Mersebach H, Rasmussen S, Bergenstal RM. Diabetes Care. 2013;36(9):2536-2542.