Use of insulin glargine U300 to improve glycaemic control in type 2 diabetes

Case 1: Suboptimal glycaemic control with NPH insulin in a patient with long-standing type 2 diabetes
History and presentation
A 66-year-old female with a 20-year history of type 2 diabetes (T2D) presented with suboptimal glycaemic control. Her comorbidities included minor coronary artery disease, meta­bolic dysfunction–associated steatot­ic liver disease (MASLD), and chron­ic hepatitis B (HBV) carrier status. She had a body mass index (BMI) of 34.7 kg/m², blood pressure (BP) of 132/56 mm Hg, and LDL-cholesterol (LDL-C) level of 1.5 mmol/L.

At presentation, her glucose-lowering regimen comprised met­formin 2 g/day (500/500/1,000 mg TDS), neutral protamine Hagedorn (NPH) insulin 20 units OM and 12 units PM, and subcutaneous semaglutide 1 mg once weekly. She had been re­ceiving insulin therapy for 13 years.

Her HbA_1c level was 7.5 per­cent. Self-monitoring of blood glu­cose (SMBG) indicated persistent hyperglycaemia throughout the day, with morning glucose lev­els of 6–8 mmol/L and preprandial readings of 8–9 mmol/L. No docu­mented episodes of hypoglycaemia were reported.

Treatment and response
In view of the suboptimal HbA_1c, the patient was switched from NPH insulin to insulin glargine 300 units/ mL (Gla-300) at a dose of 30 units once daily. After 3 months, HbA_1c decreased to 6.6 percent and re­mained stable thereafter. (Table 1) Preprandial SMBG also improved to 6–7 mmol/L. No hypoglycaemic ep­isodes occurred, and body weight remained stable at 80.1 kg.

Case 2: Reduced hypoglycaemic episodes following switch from NPH insulin to Gla-300
History and presentation
A 78-year-old female with a 30- year history of T2D (diagnosed in 1995) presented with glucose variability and symptomatic hypoglycaemia. She had been on insulin therapy since 2010. Her medical history included hyperten­sion, hypercholesterolaemia, diabetic retinopathy, MASLD, HBV carrier sta­tus, and osteoarthritis of the knees.

At presentation, her BMI was 26.6 kg/m², BP was 129/51 mm Hg, LDL-C was 1.5 mmol/L, and estimat­ed glomerular filtration rate (eGFR) was 64 mL/min/1.73 m². HbA_1c was 7.5 percent.

Her antidiabetic treatment consist­ed of metformin 1 g twice daily, gli­clazide 40 mg twice daily, vildagliptin 50 mg twice daily, and NPH insulin 10 units before bedtime. SMBG before lunch showed recurrent symptomat­ic hypoglycaemia characterized by dizziness and hunger, with glucose readings generally in the range of 4–7 mmol/L and a lowest documented level of 3.6 mmol/L.

Treatment and outcome
NPH insulin was replaced with an equivalent dose of Gla-300 (10 units). At 4-month follow-up, HbA_1c remained stable at 7.5 percent, (the individual­ized target for this patient), with no fur­ther hypoglycaemic episodes record­ed on SMBG. (Table 2)

Discussion
Treat-to-target and individualized glycaemic goals
Achieving glycaemic control is central to diabetes management, as sustained hyperglycaemia is linked to the development of acute and chronic complications. Each 1 percent reduc­tion in HbA_1c is associated with a 37 percent decrease in risk of microvas­cular complications and 21 percent decrease in risk of diabetes-related mortality.^1,2

However, intensifying glucose-lowering therapy increases the risk of hypoglycaemia, which may offset clini­cal benefits. Glycaemic targets should therefore be individualized, balancing efficacy and safety. The American Dia­betes Association (ADA) recommends an HbA_1c target of <7.0 percent for many nonpregnant adults, while less stringent targets may be appropriate for older adults, especially those with multiple comorbidities, cognitive im­pairment, or frailty.¹

Considerations for treatment selection in T2D
Choice of glucose-lowering ther­apy in T2D should consider baseline glycaemic status, body weight, co­morbidities (including chronic kidney disease [CKD] and atherosclerotic cardiovascular disease), and hypoglycaemia risk.¹

Given the progressive nature of T2D due to β-cell dysfunction, many patients will ultimately require insulin. Initiation of insulin therapy should be considered when glycaemic control remains inadequate despite noninsulin therapies, or in the presence of marked hyperglycaemia (eg, HbA_1c>10 per­cent or blood glucose ≥16.7 mmol/L), regardless of disease duration.¹

Optimizing basal insulin therapy
The primary role of basal insulin is to control fasting glucose levels, par­ticularly overnight and between meals. Dose titration is guided by fasting glu­cose monitoring, following a stepwise, patient-centred approach consistent with the ADA Standards of Care, with regular incremental dose adjustments based on SMBG patterns.¹ Available options include intermediate-acting (eg, NPH insulin), long-acting (eg, Glar-100) and ultra-long-acting ana­logues (eg, Glar-300, insulin degludec [Deg]).^1,3

NPH insulin has a pronounced peak at approximately 4–6 hours af­ter administration and a duration of action of about 12 hours, which may contribute to glycaemic variability and increased hypoglycaemia risk.³

In contrast, second-generation basal insulin analogues such as Gla-300 and Deg provide >24-hour glucose-lowering activity with a flatter pharmacokinetic (PK) and pharma­codynamic (PD) profile and no pro­nounced peak, resulting in more stable insulin exposure and reduced glycae­mic variability, particularly nocturnal hypoglycaemia.^3-5

Importantly, overbasalization should be avoided during titration, particular­ly when increasing insulin doses fail to correct persistent glycaemic variabili­ty or postprandial hyperglycaemia. In such cases, addition of prandial insulin should be considered.¹

Clinical experience with Gla-300 vs NPH
Case 1 illustrates when glycaemic variability may contribute to subopti­mal HbA_1c control while on NPH insu­lin, and Gla-300’s more stable and pro­longed action profile supporting more consistent glucose control throughout the day. Switching to Gla-300 enabled safe glycaemic improvement without increasing hypoglycaemia risk. Case 2 similarly demonstrated improved gly­caemic stability and reduced hypogly­caemic episodes following the switch to Gla-300.

These observations are consistent with evidence from a meta-analysis showing that Gla-300 is associated with a lower risk of hypoglycaemia vs NPH insulin.⁶

Benefits of Gla-300 vs Deg-100
Insulin degludec 100 U/mL (Deg- 100) is another second-generation basal insulin analogue. A head-to-head clinical trial has been conducted to directly compare these two basal insulin therapies. The 24-week open-label, randomized, noninferiority BRIGHT trial (n=929) compared Gla- 300 vs Deg-100 in insulin-naïve adults with T2D inadequately controlled with oral antihyperglycaemic agents. Both basal insulin analogues achieved sim­ilar HbA_1c reductions, demonstrating noninferiority (p<0.0001). Although overall hypoglycaemia incidence and rates were comparable over the full study period, hypoglycaemia was lower with Gla-300 during the active titration phase (weeks 0–12).⁷

Lower hypoglycaemia rates with Gla-300 may translate into reduced healthcare utilization, including emer­gency department visits and hospital admissions. From a patient perspec­tive, hypoglycaemia experienced during insulin titration can negatively affect confidence in insulin therapy, particularly among insulin-naïve in­dividuals initiating insulin treatment for the first time. Importantly, higher rates of hypoglycaemia have been associated with an increased likeli­hood of insulin discontinuation in pa­tients with T2D.⁸

Conversely, reduced hypoglycae­mia may help improve patients’ con­fidence in insulin therapy, strengthen trust between patients and health­care professionals, and enhance long-term treatment adherence. In addition, reductions in hypoglycae­mic episodes may reduce the need for corrective carbohydrate intake or compensatory snacking before bedtime (both detrimental to body-weight control), and reduce noctur­nal anxiety related to hypoglycaemia, which may further support quality sleep and improve overall treatment satisfaction.

In special populations
A prespecified subgroup analy­sis of the BRIGHT trial demonstrated significantly greater HbA_1c reductions with Gla-300 vs Deg-100 in partici­pants with eGFR <60 mL/min/1.73 m² (n=96). Mean HbA_1c decreased from 8.58 to 6.94 percent with Gla- 300 and from 8.30 to 7.28 percent with Deg-100 at week 24 (least squares mean difference, -0.43 per­cent. Hypoglycaemia risk was similar between Gla-300 and Deg-100 in this subgroup.⁹

A post hoc analysis of patients aged ≥70 years (n=161) in the BRIGHT trial also showed great­er HbA_1c reduction with Gla-300 vs Deg-100, supporting its utility in old­er populations where hypoglycaemia risk is a major concern. Mean HbA_1c decreased from 8.54 to 6.96 percent with Gla-300 and from 8.44 to 7.24 percent with Deg-100 at week 24 (least squares mean difference, -0.34 percent).^1,10

These findings are clinically rele­vant in patients with T2D and comor­bid CKD, where treatment options are limited and hypoglycaemia avoid­ance is particularly important.⁹

Practical advantages of Gla-300
Gla-300 is administered as a convenient once-daily injection. Compared with other available bas­al insulins in Hong Kong, Gla-300 is delivered in one-third the injection volume, resulting in a more compact subcutaneous depot with a smaller surface area. This contributes to a slower and more gradual insulin re­lease. The reduced injection volume may also improve tolerability, particu­larly in patients requiring higher insu­lin doses.^4,11

Unlike NPH insulin, which may need to be administered twice daily and requires more consistent dosing schedules due to its shorter duration of action and greater glycaemic vari­ability, Gla-300 provides greater flexi­bility in dosing time. It may be admin­istered within ±3 hours of the usual injection time without compromising efficacy or safety.¹¹

Key takeaways
Timely initiation and optimization of basal insulin are essential in pa­tients with T2D who remain above glycaemic targets despite noninsulin therapy. Compared with NPH insu­lin, second-generation basal insulin analogues such as Gla-300 provide more stable and prolonged glucose-lowering activity with reduced gly­caemic variability and lower hypogly­caemia risk, including during titration. In the presented cases, switching to Gla-300 improved glycaemic stability while minimizing hypoglycaemia. Ev­idence from the BRIGHT trial further supports the use of Gla-300, par­ticularly in older adults and patients with CKD, where minimizing hypo­glycaemia, maintaining treatment ad­herence, and supporting confidence in insulin therapy are key clinical priorities.

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