Endocrinology

Treatment and Daily Management

At a Glance

Treatment for INSR deficiency must be individualized because insulin resistance can coexist with dangerous low blood sugar. Care focuses on planned feeding, glucose and ketone monitoring, specialist-directed medicines, and a clear sick-day plan to prevent emergencies.

Living with an INSR-related syndrome requires a unique approach to medical care. Because the core problem is altered insulin receptor signaling, treatment requires careful individualization. There is currently no cure, so management focuses on stabilizing blood sugar, supporting growth, and preventing metabolic crises ^[1].

Do not start, stop, or change any medication—including insulin or metformin—without direct instruction from your specialist.

Individualizing Conventional Treatments

In most forms of diabetes, the goal is to give more insulin or make the body more sensitive to it. In INSR deficiency, these strategies must be carefully tailored:

Insulin: Because the “locks” (receptors) are altered, giving massive doses of insulin may not open the doors to cells effectively, though it is absolutely essential during a DKA crisis ^[2].
Metformin: While metformin is commonly used in milder forms like Type A insulin resistance, some patients have experienced postprandial hypoglycemia while taking it ^[3]^[4].

Off-Label and Specialized Pharmacological Options

Specialists may use several “off-label” medications (approved for other conditions but used here based on expert consensus and case studies). These are not routine treatments for all INSR disorders.

1. Bypassing the Receptor: rhIGF-1 (Mecasermin)

The IGF-1 receptor is a “cousin” to the insulin receptor. Because it is often still working, giving recombinant human IGF-1 (rhIGF-1) can help bypass the broken insulin receptor to lower blood sugar and support growth ^[5]^[6].

Evidence: Some patients experience better fasting tolerance and improved growth ^[7]. In severe cases, delivery via an insulin pump has been used in case reports, but it is not a standard option ^[8].
Limitations: It is officially approved for severe primary IGF-1 deficiency. It carries a risk of causing hypoglycemia itself, and responses vary widely ^[6].

2. Removing Sugar via the Kidneys: SGLT2 Inhibitors

SGLT2 inhibitors (such as empagliflozin) work by telling the kidneys to flush excess sugar out through the urine. Crucially, this process does not require insulin ^[9].

Evidence: Individual case reports show improved time-in-range ^[10]^[11].
The “Sick-Day” Warning: These drugs carry a major risk of euglycemic DKA—a dangerous acid buildup in the blood that can happen even when blood sugar levels look normal ^[2]^[12]. They also increase the risk of dehydration and urinary infections. They must be stopped during illness or fasting, following a strict “sick-day plan” from your doctor ^[13].

3. Metreleptin and Other Agents

Metreleptin is primarily used when there is also a severe lack of body fat (lipodystrophy) ^[14]. In some studies of Rabson-Mendenhall syndrome, it helped lower A1c ^[15]. Medications like diazoxide or lanreotide are sometimes used experimentally to stabilize insulin secretion, but they can severely worsen high blood sugars ^[16]^[17].

Daily Management: The Balancing Act

Management is a 24-hour-a-day task of preventing “spikes” while avoiding “crashes.”

Managing the “Crash” (Hypoglycemia)

Frequent Feeding: Many patients, especially infants, require feeding every 2 to 3 hours to prevent fasting hypoglycemia ^[18]^[19].
Cornstarch and Low-GI Foods: Using uncooked cornstarch (which digests very slowly) or low-glycemic-index foods can help provide a steady stream of sugar ^[19]^[20]. Uncooked cornstarch has age and tolerance limits and must be used carefully.

Carbohydrate Control

There is no universal diet for INSR deficiency. Feeding intervals and carbohydrate composition must be tailored by a metabolic/endocrine dietitian. While choosing complex carbohydrates that digest slowly can help stability ^[19], aggressive carbohydrate restriction should be avoided unless strictly supervised, as it can precipitate dangerous hypoglycemia or ketosis.

Monitoring Tools

Continuous Glucose Monitors (CGM) are vital for many families ^[9]. They provide data and alarms to alert you to dropping blood sugar ^[20]^[21]. However, they are an adjunct tool. CGMs lag during rapid rises or sudden drops. Always use a standard blood glucose meter if symptoms do not match the CGM reading. Regular monitoring for ketones is also required, especially when using SGLT2 inhibitors or during any illness ^[2]^[13].

Common questions in this guide

What is the main goal of treatment for INSR deficiency?

There is currently no cure, so care focuses on keeping blood sugar from swinging too high or too low, supporting growth, and preventing metabolic emergencies. The right plan differs from person to person and should be set by an endocrinology or metabolic specialist.

Can rhIGF-1, also called mecasermin, help someone with INSR deficiency?

RhIGF-1 may partly bypass the altered insulin receptor and has helped some people with fasting tolerance or growth. It is an off-label, specialist-directed option, responses vary, and it can itself cause hypoglycemia.

What should I know about SGLT2 inhibitors and sick days?

SGLT2 inhibitors can lower blood sugar without relying on insulin, but they can cause a dangerous acid buildup called euglycemic diabetic ketoacidosis, as well as dehydration and urinary infections. Anyone taking one needs a clinician-provided sick-day plan, including when to pause the medicine during illness or fasting and when to check ketones.

How can feeding and diet help prevent low blood sugar?

Some patients, especially infants, need food every 2 to 3 hours, and slowly digested carbohydrates or carefully used uncooked cornstarch may help provide steadier glucose. A metabolic or endocrine dietitian should individualize the plan because aggressive carbohydrate restriction can trigger hypoglycemia or ketosis.

How should a CGM be used to monitor INSR deficiency?

A CGM can show trends and alert families to falling glucose, but readings may lag during rapid changes. Check a standard blood glucose meter when symptoms do not match the CGM, and ask the care team how often to monitor ketones, especially during illness or while using an SGLT2 inhibitor.

Should insulin or metformin be changed if blood sugar is unstable?

Do not start, stop, or change either medicine without direct instructions from the treating specialist. In INSR deficiency, insulin may be essential during a diabetic ketoacidosis crisis but large doses may not work as expected, and metformin can be followed by post-meal hypoglycemia in some patients.

Get notified when new evidence is published on Hyperinsulinism due to INSR deficiency.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

Key takeaways

INSR deficiency has no cure, so treatment aims to stabilize blood sugar, support growth, and prevent metabolic crises.
Medication plans must be individualized; insulin and metformin can have different effects, and specialists may consider off-label therapies such as rhIGF-1 or SGLT2 inhibitors.
SGLT2 inhibitors can cause euglycemic diabetic ketoacidosis, dehydration, and urinary infections, so patients need clinician-directed sick-day instructions and ketone checks.
Frequent feeding, slowly digested carbohydrates or carefully used cornstarch, and dietitian guidance may help prevent hypoglycemia; aggressive carbohydrate restriction can be dangerous.
CGMs provide alerts but can lag during rapid changes, so unexpected readings or symptoms should be checked with a standard blood glucose meter.

References (21)

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2
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3
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4
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8
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9
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10
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11
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13
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21
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This page is for informational purposes only and does not constitute medical advice. Treatment of INSR-related hyperinsulinism, including medication changes and sick-day plans, must be individualized with your specialist.