Despite major advances in cardiometabolic therapies, many people with type 2 diabetes (T2D) will eventually require basal insulin. The clinical challenge is not only initiating insulin in appropriate patients but also optimizing therapy while avoiding overbasalization and minimizing treatment burden. Once-weekly basal insulins represent an important advancement that may help simplify insulin therapy for appropriate patients.
SPONSORED CONTENT BY NOVO NORDISK
The Modern Treatment Algorithm for Type 2 Diabetes
In caring for adults with type 2 diabetes (T2D), conversations about insulin often happen later than they should. For many patients, adding insulin can feel like a sign of personal failure, while clinicians may view initiation as a complex step that is easier to postpone. However, neither perspective reflects the underlying biology. T2D is progressive, and over time pancreatic beta-cell function declines, making insulin a necessary part of care for many patients. For example, UKPDS 49 highlighted that only about one-quarter of participants maintained an A1C below 7% with monotherapy at 9 years after diagnosis, illustrating that treatment must evolve as the disease advances. [1,2]
The modern T2D treatment algorithm has moved beyond focusing on glucose lowering alone. For patients with established or high risk for atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, obesity, or other metabolic comorbidities, treatment selection now prioritizes therapies with demonstrated cardiorenal, weight, and metabolic benefits. Current guidance also prefers GLP-1 receptor agonist or dual GIP/GLP-1 receptor agonist therapy before insulin for most adults who do not have severe hyperglycemia or hyperglycemic crisis. [1]
While addressing cardiovascular, renal, and weight-related comorbidities should be prioritized, achieving and maintaining glycemic targets may require insulin replacement. Basal insulin remains foundational because it works to dampen hepatic glucose release during the night and between meals.[1] The clinical task is to introduce it at the right time, titrate it toward a defined fasting glucose objective, and recognize when it has accomplished what basal insulin can reasonably accomplish.
When Basal Insulin Is the Appropriate Next Step
Basal insulin should be considered when individualized glycemic goals are unlikely to be reached with current pharmacotherapy, despite attention to adherence, access, lifestyle, and appropriate use of noninsulin therapies. The decision is particularly urgent when a patient has symptomatic hyperglycemia, catabolic features such as unintentional weight loss or ketosis, or very high blood glucose levels. Under the 2026 ADA Standards, these features — symptomatic hyperglycemia, an A1C above 10%, or glucose at or above 300 mg/dL — warrant starting insulin even when a patient is already on other agents and irrespective of how long they have had diabetes.[1]
For patients without severe hyperglycemia, insulin initiation is individualized. Even with appropriate cardiometabolic therapies, such as metformin, GLP-1 receptor agonist, dual GIP/GLP-1 receptor agonist, or an SGLT2 inhibitor, some patients remain above target as endogenous insulin secretion declines. In this setting, adding basal insulin is not a retreat from modern therapy; it is a complementary response to progressive beta-cell dysfunction. When insulin is used, current guidance supports retaining agents with cardiovascular, kidney, weight, or metabolic benefit when tolerated and clinically appropriate, while reassessing medications that increase hypoglycemia risk or add little incremental value.[1]
In practice, reluctance to start insulin often reflects a combination of patient and clinician concerns. Some patients may fear hypoglycemia, weight gain, or the complexity of an insulin regimen. Clinicians may anticipate training demands, follow-up needs, or titration uncertainty. A more productive conversation frames insulin as a tool rather than a verdict. It should include the purpose of basal insulin, the individualized fasting glucose target, the monitoring plan, recognition and treatment of hypoglycemia, and a clear schedule for reassessment. Shared decision-making also means discussing the practical differences among available basal options, including injection frequency, device characteristics, dose-conversion requirements, cost, coverage, and the patient’s confidence in following the regimen.
| Clinical vignette A 58-year-old adult with T2D is taking metformin, a GLP-1 receptor agonist, and an SGLT2 inhibitor. A1C remains 9.1%, and fasting glucose values are usually 175 to 215 mg/dL despite confirmed medication access and use. There are no catabolic symptoms, but the current regimen is unlikely to achieve the individualized goal without insulin replacement. Rather than waiting for further deterioration, the clinician introduces basal insulin with a defined fasting target, a monitoring and titration plan, and follow-up that is frequent enough to address concerns early. The existing agents are reviewed for continued cardiorenal and weight benefit rather than reflexively discontinued. |
Once-Weekly Insulins as an Emerging Therapeutic Class
Basal insulin delivery has evolved from formulations with pronounced peaks and variable duration to long-acting and ultra-long-acting analogs that provide more predictable glucose lowering effects. Once-weekly basal insulins extend that evolution by distributing basal insulin activity across a 7-day dosing interval. For a person who would otherwise require one basal insulin injection every day, a once weekly basal insulin would decrease the number of scheduled basal injections from approximately 365 to 52 per year.
This difference may matter for some adults with T2D, particularly those who prefer fewer injections. However, it should not necessarily be assumed that less frequent dosing will directly improve adherence, treatment satisfaction, or glycemic outcomes for every patient. Missing a weekly dose has different implications from missing a daily dose, and the prolonged duration of action heightens the importance of accurate dose calculation, medication reconciliation, titration, glucose monitoring, and patient education.
Multiple phase 3 clinical trials have evaluated once‑weekly basal insulins in adults with T2D, including both insulin‑naive adults and those previously treated with basal insulin. Across these studies, once-weekly basal insulin regimens generally achieved A1C reductions that were noninferior to once-daily basal insulin comparators, with small A1C or time-in-range differences favoring weekly therapy in some analyses; however, results varied by formulation, study population, and trial design. A class-level systematic review and meta-analysis of 14 randomized controlled trials involving 8,487 adults with T2D found a small mean A1C difference favoring weekly therapy, a modest improvement in time in range, and no statistically significant difference in level 2 or 3 hypoglycemia. However, since these pooled estimates reflect data across different products, they should not be interpreted as evidence of the efficacy or safety of any individual formulation. Additionally, because trial level results differed, and each once‑weekly insulin has distinct pharmacokinetics, dosing, and clinical evidence, findings should not be assumed to apply uniformly across the class.[6-8,11,12,19]
Selected early-phase and clinical pharmacology studies have also explored higher-risk circumstances such as prolonged fasting, exercise, and inadvertent excess dosing. In one study of 54 adults with T2D, hypoglycemia was evaluated during prolonged fasting, fasting combined with exercise, and double dosing of the once-weekly basal insulin efsitora alfa. Most events were level 1 hypoglycemia, level 2 hypoglycemia was infrequent, and no severe hypoglycemic episodes were observed.[13]
In a separate study of 30 physically active adults with T2D, time below range remained low during a standardized exercise challenge and an 18-hour fast while at steady state with insulin icodec, with no clinically significant or severe hypoglycemia reported, although some participants required protocol-directed glucose rescue.[20] Another randomized crossover study evaluating double or triple doses of once-weekly insulin icodec in adults with T2D found low rates of clinically significant hypoglycemia, no severe hypoglycemic events, and physiological responses to hypoglycemia were similar to those observed with double and triple doses of insulin glargine U100.[21]
In summary, once-weekly basal insulins may reduce injection burden while providing glycemic efficacy comparable to once-daily basal insulin in appropriately selected adults with T2D. Treatment selection should be individualized according to hypoglycemia risk, cognitive and functional status, the reliability of medication-taking routines, the ability to recognize and respond to glucose excursions, concurrent therapies, access, and patient preference. Individual formulations within the class differ in pharmacokinetics, dose-conversion methods, concentration, delivery device, titration algorithm, clinical evidence, and safety profile. Evidence, dosing instructions, and risk-management strategies should not be assumed to transfer from one formulation to another.
| U.S. regulatory status as of September 2026 Insulin icodec-abae was approved by the FDA on March 26, 2026, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is a U-700 insulin administered once weekly. Dosing, switching, missed-dose instructions, warnings, and precautions are product-specific; clinicians should consult the current Prescribing Information.[14] Insulin efsitora alfa-gobe was approved by the FDA on September 24, 2026, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is available as U-500 and U-1000 formulations administered once weekly. Dosing, switching, missed-dose instructions, warnings, and precautions are product-specific; clinicians should consult the current Prescribing Information.[22] |
Clinical Considerations with Once-Weekly Basal Insulins
| Changes in physical activity Exercise can increase glucose utilization during and after activity. Counsel patients to review expected activity changes, monitor glucose more closely when risk is elevated, carry rapid-acting carbohydrate, and recognize delayed hypoglycemia. Published analyses of once-weekly insulin studies have not shown a consistent additional physical activity-attributed hypoglycemia signal compared with daily basal insulin, but these data do not remove the need for individualized precautions. [13,15,20] |
| Planned fasting, procedures, or surgery Plan in advance. Document the exact insulin product, concentration, weekly dose, date and time of the last dose, and the next scheduled dose. Coordinate outpatient and procedural teams, consider CGM and point-of-care glucose needs, review other glucose-lowering therapies – including SGLT2 inhibitors – and establish a hypoglycemia and hyperglycemia response plan. Because weekly basal insulin remains active across several days, clinicians should use product-specific guidance rather than applying a generic “hold the basal dose” rule. In the small prospective study described above, CGM-detected time below 54 mg/dL was low at 0.2% ± 0.8% of the 18-hour fast, and no clinically significant or severe hypoglycemic episodes were reported. However, intravenous glucose was administered to 15 of 30 participants under the study protocol when plasma glucose fell below the prespecified threshold of 72 mg/dL. These results reinforce the importance of close monitoring and a predefined rescue plan; they do not establish that prolonged fasting or peri-procedural NPO status is risk-free. [20] |
| Acute illness or disrupted nutrition Illness may increase or decrease insulin requirements and can change hydration, oral intake, and ketone risk. Increase glucose monitoring as clinically appropriate, assess hydration and ketones when indicated, and give patients clear thresholds for contacting the care team. Do not improvise short-term changes to a weekly basal dose without considering the product’s long action. For both currently approved once-weekly insulins, the respective Prescribing Information advises against adjusting the weekly dose during acute illness or short-term changes in physical activity or usual diet. Other individualized measures, including adjustments to glucose intake or other glucose-lowering medications, and close glucose monitoring may be needed. Clinicians should consult the current product-specific Prescribing Information.[14,22] |
| Hospital admission and discharge Medication reconciliation must capture more than the word “insulin.” Record the product, concentration, units, dosing frequency, last administration date, next due date, and the source used to verify the history. Hospitals should develop protocols for inpatient management and care transitions because a once-weekly dose given before admission may remain clinically active throughout the stay, and duplicate dosing at admission or discharge could have prolonged consequences. Published practical guidance and analyses of hospitalizations in once-weekly insulin trials can inform local protocol development, but institution-specific policies and current labeling remain essential. [16-18] |
Understanding and Recognizing Overbasalization
Overbasalization occurs when basal insulin continues to be escalated beyond the amount needed to address fasting and between-meal hyperglycemia, often to correct residual hyperglycemia driven mainly by postprandial glucose excursions. The concept is clinically important because basal insulin is highly effective at its intended job, but it is not a substitute for prandial coverage or other strategies that address meal-related glucose.
The clearest pattern is a fasting glucose at or near the individualized target while A1C remains above target. CGM or structured self-monitoring may show substantial post-meal excursions, a large bedtime-to-morning glucose decline, overnight or fasting hypoglycemia, or wide glycemic variability. Another warning is repeated dose escalation without meaningful improvement in either fasting glucose or A1C. When the signal is “more insulin” but the response is flat, the next step should be diagnostic reassessment, not automatic titration.
A basal dose around 0.5 units/kg/day is best treated as a checkpoint, not a diagnosis or a hard ceiling. Dose-response analyses have shown diminishing glycemic benefit and greater weight gain as basal insulin doses rise above approximately 0.5 units/kg/day, which supports reassessing the regimen as the dose approaches or exceeds that range. [3] Some practical definitions and research studies have used a dose greater than 0.5 units/kg/day together with an elevated A1C to identify possible overbasalization. [4] Current ADA guidance, however, emphasizes clinical patterns – including a significant bedtime-to-morning or postprandial-to-preprandial glucose differential, hypoglycemia, and high variability – rather than relying on dose alone.[1] Weekly basal insulin should not be initiated by improvising a daily-dose multiplication or by transferring a daily titration habit to a weekly formulation.
Some insulin-resistant adults require more than 0.5 units/kg/day to control fasting glucose and are not overbasalized. Conversely, a patient can experience nocturnal hypoglycemia or a pronounced overnight drop in glucose at a lower weight-based dose. If the latter occurs, this should prompt further investigation of the dose, followed by closer evaluation of glucose patterns, safety profile, and treatment response.
It is also essential to distinguish true overbasalization from apparent insulin resistance caused by inconsistent delivery. Before concluding that a patient needs a higher dose, review:
• whether doses are being taken at the prescribed frequency;
• injection timing, priming, technique, site rotation, or injections into areas of lipohypertrophy;
• storage conditions and device function;
• access interruptions or intentional rationing;
• nutrition patterns, alcohol use, glucocorticoids, acute illness, and other contributors to hyperglycemia; and
• CGM or meter data in relation to the patient’s reported dosing history.
A history of missed basal insulin doses warrants careful assessment before transitioning from a daily to a once-weekly basal insulin. In individuals who do not consistently administer their prescribed daily basal insulin, relying solely on the prescribed dose to determine the starting weekly dose may overestimate prior insulin exposure and increase the risk of overbasalization. Therefore, consideration of actual insulin use patterns, recent glycemic trends, and hypoglycemia history may help inform dose selection in accordance with product-specific prescribing recommendations. Because once-weekly basal insulin has a distinct dosing and titration approach, daily-dose extrapolation or application of daily titration practices may result in excessive basal insulin exposure.
The practical optimization sequence is straightforward:
1. Define an individualized fasting glucose target and the glucose data that will guide titration.
2. Use trends rather than isolated readings, recognizing that the appropriate reassessment interval depends on the formulation and its pharmacokinetics.
3. Titrate until fasting glucose is controlled without unacceptable hypoglycemia.
4. Reassess A1C, CGM metrics, bedtime-to-morning change, postprandial patterns, weight, and treatment burden.
5. Stop escalating basal insulin when the fasting target has been achieved, or further escalation could increase the risk of hypoglycemia, excessive drop in glucose overnight, or no additional/meaningful glycemic benefit is expected.
Continuing to increase basal insulin after that point can raise the risk of nocturnal and fasting hypoglycemia, weight gain, and frustration while leaving the actual problem – often postprandial hyperglycemia – untreated. The longer action of a weekly basal formulation makes disciplined reassessment especially important because an excessive dose cannot be quickly withdrawn from the body.
| Clinical pearls for avoiding overbasalization • Target fasting glucose first, using an individualized goal. • Base decisions on trends, not a single morning value. • Review A1C and the broader glycemic pattern, preferably with CGM when available. • Ask about nocturnal, fasting, and activity-related hypoglycemia at every titration visit. • Verify adherence and injection technique before labeling the patient insulin resistant. • Reconcile the dose actually taken before calculating a switch to a weekly formulation. • Intensify the component of the regimen that matches the physiology of the remaining hyperglycemia. |
What to Do When Glycemic Goals Are Not Met
Once fasting glucose is at target, persistent elevation in A1C should trigger a structured evaluation rather than further basal escalation.
First, confirm that the apparent fasting control is real and durable. Review CGM or self-monitored values over enough days to distinguish a pattern from chance. Look for overnight declines, early-morning lows, rebound eating, or variability that an average fasting value may conceal.
Second, verify insulin delivery and the medication list. Reassess adherence, injection technique, storage, access, and the use of agents that may increase hypoglycemia. Consider whether a new illness, glucocorticoid exposure, shift-work schedule, or major change in nutrition or activity is distorting the pattern.
Third, identify postprandial hyperglycemia. CGM is particularly useful because it can show which meal produces the largest and most sustained excursion, whether hyperglycemia is present throughout the day, and whether the patient is already spending meaningful time below range. When CGM is not available, structured checks before and after selected meals can answer many of the same questions.
Fourth, choose an intervention that addresses the identified physiology and aligns with the patient’s priorities. Options may include optimizing or adding a GLP-1 receptor agonist or dual GIP/GLP-1 receptor agonist, using a fixed-ratio basal insulin/GLP-1 receptor agonist combination when appropriate, introducing targeted mealtime insulin, strengthening nutrition and activity interventions, or using another guideline-consistent intensification strategy. If prandial insulin is added and meal coverage increases substantially, the basal dose may need to be reduced to limit hypoglycemia. [1]
Finally, set a reassessment date and define what success will look like. A1C, CGM metrics, hypoglycemia, weight, treatment burden, and the patient’s experience all matter. Intensification should not be a one-way ratchet; deintensification is appropriate when glucose toxicity resolves, weight changes, hypoglycemia develops, or the regimen becomes more complex than necessary.
Using Innovations Thoughtfully
As type 2 diabetes progresses, many patients will require basal insulin despite the availability of numerous effective glucose-lowering therapies. The goal is not simply to initiate insulin, but to use it thoughtfully, titrate it appropriately, avoid overbasalization, and select options that align with patients’ needs and preferences. Once-weekly basal insulin therapies represent an evolution in simplifying insulin treatment while maintaining the focus on individualized glycemic management.
| Important note This disease-state educational article is intended for U.S. health care professionals. It is not a substitute for clinical judgment or product-specific prescribing information. Consult current prescribing information for any therapy discussed. This article was developed and funded by Novo Nordisk. Author disclosures: Nathan Laney, MD, and Daniela Fernandez, PharmD, are employees of Novo Nordisk Inc. |
References
- American Diabetes Association Professional Practice Committee for Diabetes. 9. Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S183-S215. doi:10.2337/dc26-S009.
- Turner RC, Cull CA, Frighi V, Holman RR; UK Prospective Diabetes Study Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281(21):2005-2012. doi:10.1001/jama.281.21.2005.
- Umpierrez GE, Skolnik N, Dex T, Traylor L, Chao J, Shaefer C. When basal insulin is not enough: a dose-response relationship between insulin glargine 100 units/mL and glycemic control. Diabetes Obes Metab. 2019;21(6):1305-1310. doi:10.1111/dom.13653.
- Cowart K, Updike WH, Pathak R. Prevalence of and characteristics associated with overbasalization among patients with type 2 diabetes using basal insulin: a cross-sectional study. Clin Diabetes. 2021;39(2):173-175. doi:10.2337/cd20-0080.
- Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022: a consensus report by the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2022;45(11):2753-2786. doi:10.2337/dci22-0034.
- Rosenstock J, Bain SC, Gowda A, et al; ONWARDS 1 Trial Investigators. Weekly icodec versus daily glargine U100 in type 2 diabetes without previous insulin. N Engl J Med. 2023;389(4):297-308. doi:10.1056/NEJMoa2303208.
- Philis-Tsimikas A, Asong M, Franek E, et al. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomized, open-label, treat-to-target trial. Lancet Diabetes Endocrinol. 2023;11(6):414-425. doi:10.1016/S2213-8587(23)00093-1.
- Bajaj HS, Asbjornsdottir B, Bari TJ, Begtrup K, Vilsboll T, Rosenstock J. Once-weekly insulin icodec compared with daily basal insulin analogues in type 2 diabetes: participant-level meta-analysis of the ONWARDS 1-5 trials. Diabetes Obes Metab. 2024;26(9):3810-3820. doi:10.1111/dom.15726.
- Bajaj HS, Bergenstal RM, Christoffersen A, et al. Once-weekly insulin icodec with dosing guide app versus once-daily basal insulin analogues in insulin-naive type 2 diabetes (ONWARDS 5): a randomized trial. Ann Intern Med. 2023;176(11):1476-1485. doi:10.7326/M23-1288.
- Polonsky WH, Benamar M, Carstensen L, et al. Improved treatment satisfaction with once-weekly insulin icodec compared with once-daily basal insulin in individuals with type 2 diabetes. Diabetes Res Clin Pract. 2024;217:111885. doi:10.1016/j.diabres.2024.111885.
- Wysham C, Bajaj HS, Del Prato S, et al; QWINT-2 Investigators. Insulin efsitora versus degludec in type 2 diabetes without previous insulin treatment. N Engl J Med. 2024;391(23):2201-2211. doi:10.1056/NEJMoa2403953.
- Rosenstock J, Bailey T, Connery L, et al; QWINT-1 Trial Investigators. Weekly fixed-dose insulin efsitora in type 2 diabetes without previous insulin therapy. N Engl J Med. 2025;393(4):325-335. doi:10.1056/NEJMoa2502796.
- Heise T, Andersen G, Pratt EJ, et al. Frequency and severity of hypoglycemia under conditions of increased hypoglycemic risk with insulin efsitora alfa versus insulin glargine treatment in participants with type 2 diabetes. Diabetes Ther. 2024;15(8):1785-1797. doi:10.1007/s13300-024-01605-7.
- Novo Nordisk Inc. Awiqli (insulin icodec-abae) injection, for subcutaneous use. U.S. Prescribing Information. Revised March 2026.
- Riddell MC, Heller S, Carstensen L, Pagliaro Rocha TM, Kehlet Watt S, Woo VC. The effect of once-weekly insulin icodec versus once-daily basal insulin on physical activity-attributed hypoglycemia in type 2 diabetes: a post hoc analysis of ONWARDS 1-5. Diabetologia. 2025;68(7):1416-1422. doi:10.1007/s00125-025-06414-6.
- Philis-Tsimikas A, Aberle J, Bajaj H, et al. Clinical use of once-weekly insulin icodec: translating clinical trial data into practical guidance for diabetes management. Drugs. 2025;85(10):1253-1268. doi:10.1007/s40265-025-02201-0.
- Philis-Tsimikas A, Bache JK, Fu A, Kellerer M, Salvesen-Sykes K, Bain SC. Insights on hospitalisations from the phase 3a ONWARDS 1-6 trials of once-weekly insulin icodec. Diabetes Ther. 2025;16(8):1615-1631. doi:10.1007/s13300-025-01745-4.
- Xu K, Hardin K, Lenox-Riccelli D, Amin AN. Insulin icodec: a once-weekly basal insulin on the horizon for diabetes management with implications for hospital care transitions. Health Sci Rev. 2026;18:100258. doi:10.1016/j.hsr.2026.100258.
- Raptis D, Chiotis S, Papamichalis T, Bekiari E, Tsapas A, Karagiannis T. Efficacy and safety of once-weekly basal insulin analogs versus daily basal insulin analogs in adults with type 2 diabetes: a systematic review and meta-analysis. Curr Diab Rep. 2026;26(1):16. doi:10.1007/s11892-026-01628-3.
- Pieber TR, Bajaj HS, Fluhr G, Klein KR, Pagliaro Rocha TM, Sourij H, et al. Exercise or fasting in individuals with type 2 diabetes receiving once-weekly basal insulin icodec. Diabetes Obes Metab. Published online July 1, 2026. doi:10.1111/dom.71050.
- Pieber, T.R., Arfelt, K.N., Cailleteau, R. et al. Hypoglycaemia frequency and physiological response after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100 in type 2 diabetes: a randomised crossover trial. Diabetologia 66, 1413–1430 (2023). https://doi.org/10.1007/s00125-023-05921-8.
- Eli Lilly and Company. Onswik (insulin efsitora alfa-gobe) injection, for subcutaneous use. U.S. Prescribing Information. Initial U.S. approval: 2026.
