AWAN Clinic

15/05/2026

𝗜𝗻𝘀𝘂𝗹𝗶𝗻 𝗜𝗰𝗼𝗱𝗲𝗰

Ultra-long acting basal insulin analog designed for once-weekly administration.

Awiqli (insulin icodec) is now FDA approved in the United States.

The FDA approved it in March 2026 as the first once-weekly basal insulin for adults with type 2 diabetes.

Key Feature

➤ Longest-acting basal insulin
➤ Duration of action ≈ 196 hours (~8 days)
➤ Provides stable and sustained basal insulin coverage
➤ Designed to reduce injection frequency and improve adherence

Comparison with other Basal Insulins

➤ Insulin Degludec
Ultra-long acting
Duration ≈ 42 hours
Once-daily dosing

➤ Insulin Glargine U100
Long acting
Duration ≈ 24 hours
Once-daily dosing

➤ Insulin Glargine U300
Long acting
Flatter and prolonged profile
Once-daily dosing

➤ NPH Insulin
Intermediate acting
Duration ≈ 12–18 hours
Usually twice-daily dosing

Advantages

➤ Once-weekly injection convenience
➤ Improved treatment adherence
➤ Reduced injection burden
➤ More stable glucose control
➤ Lower glycemic variability
➤ Potential reduction in nocturnal hypoglycemia

Clinical Use

➤ Type 2 Diabetes Mellitus
➤ Investigational/expanded use in selected Type 1 Diabetes patients
➤ Intended for patients requiring long-term basal insulin therapy

Adverse Effects

➤ Hypoglycemia
➤ Injection-site reactions
➤ Weight gain
➤ Lipodystrophy with repeated injections at same site

09/05/2026

For 50 years, eggs were treated like a cardiovascular threat. The 1960s dietary guidelines capped cholesterol intake at 300mg per day. Two eggs put you at the limit. The advice moved millions away from the food, and away from a nutrient profile we didn't fully appreciate at the time.

A new study from Loma Linda University followed 39,498 adults age 65 and older for 15.3 years. The team linked Adventist Health Study-2 dietary records with Medicare diagnoses. Over that window, 2,858 participants developed Alzheimer's disease.

The dose-response was clean.
Eating eggs 1 to 3 times a month: 17% lower incidence vs never-eaters.
2 to 4 per week: 20% lower.

5 or more per week, roughly one a day: 27% lower.
The mechanism story isn't new, but the cohort scale and 15-year follow-up are. Eggs are the densest natural source of choline in the American diet. One large egg supplies roughly 33% of the daily choline requirement. Choline is the substrate for acetylcholine, the neurotransmitter that drops in Alzheimer's. Donepezil, the most prescribed Alzheimer's drug, works by blocking acetylcholine breakdown. The disease is partly defined by cholinergic neuron loss.

Egg yolk also delivers lutein and zeaxanthin. These are the only two carotenoids that cross the blood-brain barrier and accumulate in cortical tissue. Higher tissue levels track with better processing speed and memory across multiple older-adult cohorts. Yolk also contains DHA, primarily in phospholipid form. Phospholipid DHA enters the brain more efficiently than DHA in triglyceride form, which is the dominant form in fish oil capsules.

Now the caveats, because they matter.
This is observational. Causation cannot be drawn from a cohort study. The Adventist Health Study-2 cohort skews heavily vegetarian and health-conscious, so people who eat eggs in this cohort do not look like the average American egg-eater. The "never eats eggs" comparison group is largely vegan, which is its own dietary pattern with its own complications. Reverse causation also has to be considered. People in early Alzheimer's often change eating patterns before diagnosis. Some of the apparent protection could be that healthier brains keep eating eggs, not the other way around.

The mechanism story I outlined above is supported by adjacent literature, not by this paper. The study did not measure choline status, lutein levels, or DHA in tissue. It measured eggs in, dementia out.

What we can say honestly: in a 40,000-person cohort followed for 15 years, egg intake tracked with substantially lower Alzheimer's incidence in a dose-response pattern. The mechanism is biochemically plausible, supported by other lines of evidence, and consistent with what we know about acetylcholine and brain carotenoid status. The randomized trial that would prove causation has not been run.

The practical version: if you are over 50 and not allergic, eating an egg most days has stronger evidence behind it for brain health than most products marketed for the same goal. Five days a week was the dose with the lowest risk in this cohort. Even 1 to 3 per month showed measurable benefit.

For 50 years the question was whether eggs were dangerous to your heart. The data behind that fear was always weaker than the guidelines made it sound, which is why the 2015 Dietary Guidelines for Americans quietly removed the 300mg cap. The brain question got asked too late.

Oh et al., J Nutr, 2026 (DOI: 10.1016/j.tjnut.2026.101541)

06/05/2026

lowers LDL by about 13 mg/dL 28 randomized trials. The mechanism gets misrepresented constantly. It does not absorb cholesterol.

It does not scrub the gut. The mechanism is purely mechanical, and understanding it explains why most other "soluble fibers" do not produce the same effect.

Psyllium is the seed husk of Plantago ovata. When it hits the small intestine and hydrates, it forms a viscous gel. That gel physically traps bile acids, the cholesterol-derived molecules your liver releases through the bile duct to emulsify dietary fat. Normally about 95% of bile acids are reabsorbed in the ileum and recycled back to the liver. The pool cycles 4 to 12 times per day, losing about 5% per pass. The recycling is efficient because synthesizing new bile acids is expensive. The substrate is cholesterol.

When psyllium disrupts that recycling, the liver loses inventory. Loss of FXR-mediated feedback upregulates CYP7A1, the rate-limiting enzyme in bile acid synthesis, which depletes the hepatic cholesterol pool. SREBP-2 activates, LDL receptors get upregulated, and hepatocytes pull LDL from circulation to refill it. Serum LDL drops. This is the same mechanism used by prescription bile acid sequestrants like cholestyramine.

Jovanovski et al. (2018, American Journal of Clinical Nutrition) pooled 28 randomized controlled trials covering 1,924 participants. The median dose was about 10.2 grams of psyllium per day. LDL fell by approximately 13 mg/dL. Non-HDL fell by approximately 15 mg/dL. ApoB, a more direct measure of atherogenic particles, fell by 0.05 g/L. The apoB evidence was graded as high quality.

Two things matter. First, the mechanism is purely mechanical. Psyllium is not metabolized, does not enter circulation, does not act on a receptor. That is why it has a clean side-effect profile and does not interact with the cytochrome P450 system the way most lipid-lowering drugs do.
Second, viscosity is the active property. Inulin is also classified as a soluble fiber under FDA rules, but inulin does not form a viscous gel. It is highly fermentable instead. The label calls them both soluble fiber, but their functional profiles share almost nothing.

The honest framing on magnitude. A 13 mg/dL drop is meaningful but modest compared to even the lowest-dose statin, which typically delivers 25 to 50 mg/dL. If your numbers are borderline and you want to avoid medication, psyllium is one of the few interventions with this level of evidence. If a statin is indicated, psyllium is not a replacement.

Practical: target around 10 grams of psyllium husk daily, taken with or just before a meal with a full glass of water. That matches the Jovanovski median. Many trials dose 7 grams two or three times per day for a larger effect. Start at 5 grams and titrate up to manage GI side effects.

Jovanovski et al., Am J Clin Nutr, 2018
McRorie & McKeown, J Acad Nutr Diet, 2017
Gonzalez, Compr Physiol, 2012

05/05/2026

05/05/2026

04/05/2026

.

03/05/2026

🧠 IMEGLIMIN — TOP 50 PEARLS
______________________________________________
🧬 Mechanism & Pharmacology
First-in-class “glimin” (new class).
Targets mitochondrial dysfunction (unique vs all DM drugs).
Dual action:
↑ glucose-dependent insulin secretion
↑ insulin sensitivity
Works on 3 organs: pancreas + liver + muscle.
Reduces oxidative stress (ROS) → protects β-cells.
Improves β-cell survival (anti-apoptotic).
Unlike sulfonylureas → no forced insulin release.
Less risk of hypoglycemia (glucose-dependent).
Improves mitochondrial respiration balance (Complex I & III).
Concept shift: “disease-modifying” not just glucose lowering.
📊 Efficacy & Glycemic Control
↓ HbA1c ~ 0.5–1% (moderate efficacy).
↓ fasting glucose + postprandial glucose.
Works better in combination therapy.
Improves glycemic variability (TIR ↑).
Effect stronger in early diabetes (β-cell preservation).
Less potent than GLP-1 RA / SGLT2i.
Comparable to DPP-4 inhibitors in effect.
No significant weight loss effect.
Neutral effect on lipid profile.
May improve hepatic glucose output.
💊 Indications & Position (ADA / ESC thinking)
Approved (Japan 2021) for Type 2 DM.
Not yet strongly included in ADA/ESC main algorithms.
Consider when:
metformin intolerance
add-on therapy
Useful in Asian phenotype (low β-cell reserve).
Can combine with:
metformin
DPP-4 inhibitors
insulin
Not first-line in guidelines (yet).
Potential role in CKD patients (safe profile emerging).
No strong CV outcome data → NOT preferred in ASCVD/HF (unlike SGLT2i/GLP1).
❤️ Cardiovascular & Renal Pearls
No proven CV mortality benefit.
Likely cardio-neutral.
No fluid retention (good vs TZDs).
Early signals → possible cardio-metabolic benefit (not confirmed).
Safe in heart failure (limited data).
No increase in lactate (unlike metformin concern).
⚠️ Side Effects & Safety
Generally well tolerated.
Most common: GI upset (mild).
Hypoglycemia risk → low.
No weight gain.
No edema.
Safe liver profile.
No major serious adverse events in trials.
Caution with:
severe renal impairment (data limited)
Combination with metformin → ↑ GI side effects.
💡 Dosing & Practical Use
Usual dose: 1000 mg BID (total 2000 mg/day).
Oral, twice daily.
No titration complexity.
Take with food → ↓ GI symptoms.
No strict hypoglycemia monitoring needed.
🧠
KEY DIFFERENCE:
Metformin → ↓ hepatic glucose
Imeglimin → mitochondrial + β-cell protection

“improves mitochondrial function + insulin secretion” → Imeglimin
🚨 SUMMARY
Mechanism: mitochondrial modulator (unique)
Effect: moderate HbA1c ↓ + β-cell protection
Hypoglycemia: LOW
Weight: neutral
CV benefit: NOT proven

03/05/2026

02/05/2026

There is no role for routine testing for insulin, C-peptide, or proinsulin in most patients with diabetes. Differentiation between type 1 and type 2 diabetes may be made in most cases on the basis of the clinical presentation and the subsequent course. These assays are useful primarily for research purposes. Occasionally, C-peptide measurements may help distinguish type 1 from type 2 diabetes in ambiguous cases, such as patients who have a type 2 phenotype but present in ketoacidosis.

ADA Position Statement Executive Summary 2011 I am of the view that the confidence of the patient is very important and this distinctive teat is very important

30/04/2026

کیا آپ ان لوگوں میں سے ہیں جو وزن کم کرنے کے لئے۔۔۔۔
صبح ایک انڈا کھاتے ہیں
دوپہر کو ایک کھیرا،
رات کو چکن پیس
اور پھر آدھی رات کو کچن میں جا کر دو روٹیاں، سالن کی پلیٹ، بریانی، کیک اور اس سب کو ہضم کرنے کیلئے ایک بوتل پیتے ہیں تب کہیں جا کر دن بھر کی کمزوری ختم ہوتی ہے اور نیند آتی ہے
یہ ان کے ساتھ ہوتا ہے جو خود کو بھوکا رکھ کر وزن کم کرنے کی کوشش کرتے ہیں
جب ضرورت سے انتہائی کم خوراک ملے تو جسم فائیٹ اینڈ فلائیٹ موڈ میں چلا جاتا ہے
اس کے 2 نقصان ہوتے ہیں
ایک تو جب بھی آپ کو کھانا نظر آئے گا ، آپ خود پر کنٹرول کھو دیں گے اور بہت زیادہ کھانا اچانک کھا جائیں گے

دوسرا میٹابولزم سست ہو جاتا ہے۔ کم کیلوریز لینے کے باوجود وزن کم نہیں ہو گا کیونکہ جسم اس موڈ میں سمجھتا ہے کہ خوراک کی سپلائی کسی بھی وقت بند ہو سکتی ہے تو جسم کی چکنائی کو محفوظ رکھنا ہے تاکہ برے وقت میں جب بہت دن خوراک نہیں ملے گی جسم اس چکنائی سے توانائی حاصل کرے گا

اپنے جسم کو فائیٹ اینڈ فلائیٹ موڈ سے نکالنے کے لیے آپ کو دن بھر اتنا کھانا ہو گا کہ جسم کو ضروری توانائی بھی ملے ، بے ہنگم بھوک نہ لگے اور وزن بھی کم ہو