Metformin (brand names include Glucophage, Fortamet, Glumetza) is the most widely prescribed medication for Type 2 diabetes worldwide. It belongs to a class of drugs called biguanides.
Here is a comprehensive breakdown of what it is, how it works, and what you need to know if you are taking it.
1. Primary Uses
Type 2 Diabetes: It is the first-line medication recommended for lowering blood sugar levels. It is often used alone or in combination with other drugs (like insulin).
Prediabetes (Off-label): Doctors often prescribe it to prevent the progression from prediabetes to full Type 2 diabetes, particularly in people with a high BMI.
Polycystic Ovary Syndrome (PCOS) (Off-label): It helps lower insulin levels and androgen (male hormone) levels, which can help regulate menstrual cycles and improve fertility/ovulation.
Gestational Diabetes: Sometimes used during pregnancy when insulin is not an option or not preferred, though insulin remains the gold standard.
2. How It Works
Metformin does not increase the amount of insulin your body makes (so it rarely causes low blood sugar/hypoglycemia on its own). Instead, it works in three main ways:
Stops the Liver: It reduces the amount of sugar (glucose) your liver produces and releases into your bloodstream.
Boosts Sensitivity: It makes your muscle tissue more sensitive to insulin, allowing your cells to use glucose more effectively.
Reduces Absorption: It slightly decreases the amount of sugar your gut absorbs from the food you eat.
3. Side Effects
Common (The "Metformin Tummy"):
The most common complaints are digestive. These usually happen when you first start the drug and often go away after a few weeks.
Diarrhea
Nausea/Vomiting
Stomach cramps/bloating
Metallic taste in the mouth
Serious (Rare):
Lactic Acidosis: A dangerous buildup of lactic acid in the blood. This is very rare (approx. 1 in 30,000 users) but can be fatal. Symptoms include extreme fatigue, muscle pain, difficulty breathing, and slow heart rate. It is mostly a risk for people with kidney or liver failure.
Vitamin B12 Deficiency: Long-term use can block the absorption of Vitamin B12. Your doctor may monitor your levels periodically.
4. Important Warnings & Contraindications
Kidney Function: Metformin is cleared by the kidneys. If you have severe kidney disease (typically eGFR < 30 mL/min), you cannot take it because it increases the risk of lactic acidosis.
CT Scans/Contrast Dye: If you are having an imaging scan that uses iodinated contrast dye, you may need to stop taking Metformin for 48 hours before and after the procedure to protect your kidneys.
Alcohol: Excessive alcohol intake (acute or chronic) drastically increases the risk of lactic acidosis.
Liver Disease: Used with caution or avoided in severe liver disease.
5. Practical Tips for Success
If you have been prescribed Metformin, these strategies can help minimize side effects:
Take with Food: Always take it in the middle of a meal or immediately after to buffer your stomach.
Start Low, Go Slow: Doctors usually start you on a low dose (e.g., 500mg once daily) and slowly increase it over weeks. Do not rush this titration.
Ask for Extended Release (XR/ER): If the standard "immediate release" tablets give you severe stomach upset, ask your doctor for the Extended Release version. It releases the drug slowly and is generally much gentler on the stomach.
6. Research on Longevity
You may hear Metformin discussed in "biohacking" or anti-aging circles. Some research suggests it might mimic the effects of calorie restriction and activate longevity pathways (like AMPK). However, there is currently no definitive clinical evidence that it extends lifespan in healthy humans, and it is not FDA-approved for anti-aging.
Glomerular Filtration Rate (GFR) is the primary test used to check how well the kidneys are functioning.It measures the amount of blood that passes through the glomeruli—the tiny filters in the kidneys that remove waste—every minute.
GFR is a key measure of how well your kidneys are filtering blood. It estimates how much blood (in millilitres) the kidneys filter per minute to remove waste and excess fluid.
Why GFR is Important
Your kidneys act as the body's filtration system. A high GFR means your kidneys are efficiently clearing waste, while a low GFR indicates that waste products (like creatinine) are building up in your blood because the filters are damaged or sluggish.
Standard Unit:mL/min/1.73m^2 (millilitres per minute per 1.73 square meters of body surface area).
Normal Range: Roughly 90–120mL/min for healthy adults.
In a clinical setting, you will likely see eGFR (estimated GFR) on your lab results rather than a direct measurement.
Measured GFR (mGFR): The "gold standard" involves injecting a substance, such as inulin or Iohexol, into the blood and measuring how quickly the kidneys clear it. This is a complex process and is rarely done outside of research.
Estimated GFR (eGFR): This is a calculated estimate using a mathematical formula. It typically requires:
Understanding how medications affect GFR requires looking at the "pipes" leading into and out of the kidney's filters (the glomeruli).
To keep the filtration rate steady, the kidney needs a certain amount of internal pressure. It maintains this pressure by adjusting two main vessels: the Afferent Arteriole (the "inlet" pipe) and the Efferent Arteriole (the "outlet" pipe).
1. ACE Inhibitors: Opening the "Outlet"
ACE Inhibitors (like Lisinopril or Enalapril) and ARBs (like Losartan) block Angiotensin II, a hormone that normally constricts the outlet pipe (efferent arteriole).
The Effect: These drugs cause the outlet pipe to widen (vasodilation).
Impact on GFR: Because the "exit" is now wide open, the pressure inside the filter drops. This usually causes an initial, small decrease in eGFR (a rise in creatinine).
Why doctors use them anyway: Even though GFR drops slightly at first, lowering that internal pressure protects the filters from long-term wear and tear. It’s like lowering the water pressure in a delicate pipe to prevent it from bursting over time.
2. NSAIDs: Narrowing the "Inlet"
NSAIDs (like Ibuprofen, Naproxen, or Celebrex) block Prostaglandins, which are chemicals that normally keep the inlet pipe (afferent arteriole) open.
The Effect: Without prostaglandins, the inlet pipe narrows (vasoconstriction).
Impact on GFR: Less blood can get into the filter, which reduces the pressure and lowers the GFR.
The Risk: In healthy people, the body can usually compensate. However, if you are dehydrated or already have kidney issues, NSAIDs can "starve" the kidney of blood, leading to a sudden drop in function.
3. The "Triple Whammy"
The most dangerous scenario for GFR occurs when a patient takes three types of medications together:
ACE Inhibitor/ARB: Opens the outlet (lowers pressure).
When all three are used, the kidney loses its ability to regulate its own internal pressure. This can lead to Acute Kidney Injury (AKI) because the GFR plummets dangerously low.
The idea that ancient civilisations were all connected is a popular and compelling one, often pointing to remarkable similarities in architecture, religious symbols, and cultural practices found across geographically separated regions.
While mainstream historical and archaeological consensus often favors the idea of independent development in multiple centres (like Mesopotamia, Egypt, the Indus Valley, China, and Mesoamerica), there is significant evidence of shared traits and global spread in some aspects of culture, technology, and migration.
1. Architectural and Megalithic Similarities
The most striking visual evidence often cited for a global connection is the presence of massive, complex stone structures (megaliths) and pyramidal forms across continents:
Pyramids: Structures with pyramidal shapes were built in Ancient Egypt (Great Pyramid of Giza), Mesopotamia (Ziggurats, built of mud-brick), Mesoamerica (like Chichén Itzá in Mexico), Peru, Sudan (Nubian pyramids), and even China. While their specific purpose varied—tombs for pharaohs in Egypt, temples/ritual centers in Mesoamerica, and ziggurats as temples in Mesopotamia—the common architectural impulse is notable.
Megalithic Construction: The use of enormous, precisely cut stones to build monuments is found in locations like Stonehenge (England), Göbekli Tepe (Turkey), Newgrange (Ireland), Baalbek (Lebanon), and various Andean sites. Some researchers point to the technical sophistication of these structures as evidence of a lost, advanced, unifying culture.
2. Shared Symbols and Motifs
Certain symbols and mythological motifs appear in diverse ancient cultures, which some interpret as a sign of ancient cross-cultural contact or shared knowledge:
The Sphinx: The creature with a human head and a lion's body is most famous in Egypt, but similar figures were revered in Ancient Greece, and the oldest known sphinx-like carving was found at Göbekli Tepe.
The Spiral: The spiral motif is one of the oldest symbols used in spiritual practices and is found in rock art and megalithic carvings across the globe, suggesting a universal representation of growth, evolution, or the life force.
The Pine Cone: In some esoteric interpretations, the pine cone symbol is seen in multiple cultures, including Roman, Sumerian, and Egyptian art, and is linked to the pineal gland ("Third Eye") and secret wisdom.
3. Early Trade and Cultural Diffusion
Evidence of extensive trade and contact demonstrates that civilizations were far from isolated, at least in the later periods of antiquity:
Trade Networks: The discovery of Indus Valley seals in Mesopotamia, Egyptian influence in the Aegean (Minoan Crete), and the establishment of the Silk Road connecting China to the Mediterranean world show that goods, ideas, and cultural practices (like bronze metallurgy and the wheel) spread over long distances.
Agriculture and Writing: Scholars note that while civilization arose independently in multiple locations, the rise of agriculture and, later, the invention of writing also followed paths of diffusion, suggesting contact between agrarian communities.
1. Long-Distance Trade Networks (Hard Evidence)
🔹 Indus Valley ↔ Mesopotamia (c. 2500 BCE)
Indus seals found in Mesopotamian cities (Ur, Lagash)
Mesopotamian texts refer to a land called “Meluhha” (widely accepted as the Indus region)
Trade goods included:
Carnelian beads
Cotton (rare outside India at the time)
Ivory and timber
➡️ This proves direct commercial contact between South Asia and the Middle East.
🔹 Egypt ↔ Levant ↔ Mesopotamia
Egyptian tombs contain cedar wood from Lebanon
Mesopotamian cylinder seals found in Egypt
Shared use of:
Bronze metallurgy
Weights and measures
Diplomatic gift exchange (Amarna Letters, c. 1400 BCE)
➡️ Egypt was not isolated; it was part of a Near Eastern international system.
🔹 The Silk Roads (from c. 200 BCE)
Connected:
China
Central Asia
India
Persia
Rome
Evidence:
Roman coins in India
Chinese silk in Roman graves
Buddhist texts traveling from India to China
➡️ This was a continental knowledge and trade network, not just a road.
2. Shared Technologies and Ideas
🔹 Writing Systems
Sumerian cuneiform (c. 3200 BCE)
Egyptian hieroglyphs (c. 3100 BCE)
They appeared almost simultaneously and evolved in contact zones, suggesting idea transmission, not coincidence.
🔹 Mathematics & Astronomy
Base-60 system (Mesopotamia) → still used for time (60 minutes)
➡️ Flood myths likely reflect shared human experiences after Ice Age flooding, spread via oral traditions.
4. Genetic and Linguistic Evidence
🔹 Indo-European Languages
Languages from:
India (Sanskrit)
Persia
Europe
Share:
Common grammar
Core vocabulary
Mythological structures
➡️ Indicates ancient migrations and cultural mixing, not isolation.
🔹 DNA Studies
Modern genetics shows:
Continuous human movement
Mixing across Eurasia and Africa
No population developed entirely alone
5. What Is Not Supported by Evidence
❌ A single lost global super-civilisation
❌ Atlantean world empire controlling all cultures
❌ Advanced ancient technology equal to modern tech
These ideas are popular but not supported by archaeology.
6. The Best Conclusion (Academic Consensus)
✔ Ancient civilisations were regionally distinct
✔ But they were connected by trade, migration, and shared knowledge
✔ Human history is a network, not a set of isolated islands
Ancient civilisations were not all one—but they were never truly separate.
In summary, the extent of connection is a major point of debate. Traditional archaeology highlights independent innovation followed by diffusion over time, whereas alternative theories suggest evidence of a single, highly advanced, pre-cataclysmic global civilization that influenced later cultures.
The stream of news about cancer research is constant, and while every step forward is important, the sheer volume can make individual advances feel incremental. We hear about new drugs and promising trials, but it's often hard to distinguish a small step from a giant leap.
This article cuts through the noise to highlight five breakthroughs from 2025 that represent more than just progress—they signal fundamental shifts in how scientists understand and attack cancer. These are not simply better versions of existing treatments; they are based on new, sometimes counter-intuitive, strategies for outsmarting the disease.From completely eliminating problematic proteins instead of just blocking them, to making organ preservation a primary goal of treatment, these concepts offer a glimpse into the future of oncology. They are rewriting the rules of engagement and showing that the next generation of cancer therapy will be defined by a smarter, more strategic approach to biology itself.
1. The New Strategy: Don't Just Block Cancer Proteins—Destroy Them
For decades, the standard approach in targeted cancer therapy has been to find a protein driving a tumor's growth and design a drug to inhibit, or block, its function. A new class of drugs, however, is built on a more decisive strategy: don't just block the protein, get rid of it entirely. This approach, known as targeted protein degradation, is now showing its power in the clinic.
The leading example is Vepdegestrant (ARV-471), a new oral therapy for ER-positive/HER2-negative breast cancer. It is a PROTAC (PROteolysis TArgeting Chimaera), a molecule that not only blocks the estrogen receptor (ER) that fuels these cancers but also targets it for degradation. Instead, it acts as a molecular matchmaker, using the cell’s own machinery to degrade and destroy the receptor. By recruiting the cell's natural disposal system, it marks the ER protein for complete elimination.
This is a powerful way to overcome drug resistance, a major challenge in breast cancer treatment. Many tumors develop mutations in the ESR1 gene, which allows them to resist standard endocrine therapies. The Phase 3 VERITAC-2 trial provided a clear picture of Vepdegestrant’s unique strength. In the overall trial population, the benefit was modest and did not reach statistical significance (median Progression-Free Survival of 3.8 vs 3.6 months). However, in the crucial ESR1-mutant subgroup, where resistance is most common, the results were dramatic. Vepdegestrant achieved a median Progression-Free Survival (PFS) of 5.0 months, more than doubling the 2.1 months seen with the standard-of-care drug fulvestrant (HR 0.58). The Objective Response Rate (ORR) was also more than four times higher, at 18.6% versus 4.0%.
This marks a conceptual leap from merely disrupting a cancer pathway to surgically removing its key components, a strategy designed to preempt resistance before it can begin.
2. A Surprising New Goal: Saving Organs, Not Just Lives
For certain cancers, a successful outcome has long meant removing the affected organ—a life-saving but life-altering necessity. A recent breakthrough in uveal melanoma, a rare cancer of the eye, is challenging that paradigm by showing that it's possible to treat the cancer effectively while preserving the organ and its function.
Patients with primary uveal melanoma often face surgical removal of the eye, a procedure known as enucleation. The new drug Darovasertib, a selective PKC inhibitor, represents a "genuine paradigm shift" by offering a powerful neoadjuvant (pre-surgery) treatment that can shrink tumors enough to make less radical therapies possible.
The results from the Phase 2 OptimUM-09 trial are unprecedented. Across all patients, 83% experienced measurable tumor shrinkage, and 54% achieved shrinkage of 20% or more. This translated directly into organ preservation. Among patients who were originally recommended for enucleation, treatment with Darovasertib preserved the eye in 57% of cases. For patients whose tumors shrank by at least 20%, the eye-preservation rate soared to an incredible 95%.
Even more remarkably, the treatment not only saved the eye but also protected and even improved its function. More than half of all patients in the trial experienced an improvement in their visual acuity during treatment. This redefines what a successful outcome can be, shifting the goal from just survival to include profound quality-of-life improvements. The focus is no longer simply on organ removal, but on organ preservation, demonstrating that future cancer treatments can aim to save not just the patient's life, but also its quality.
3. Immunotherapy's Two-Front War: Attacking the Tumor and Its Bodyguards
Immunotherapy has revolutionized cancer treatment, but a major obstacle remains: the Tumor Microenvironment (TME). This complex ecosystem of non-cancerous cells, including immune cells like macrophages, can form a "protective shield for the tumor," making it difficult for therapies to penetrate and for the patient's own immune system to launch an effective attack. New therapies are now being designed to fight a two-front war, simultaneously targeting the tumor and the very cells that protect it.
A novel CAR-T cell therapy from Mayo Clinic, known as MC9999, is a prime example of this new strategy. Traditional CAR-T therapies engineer a patient's T-cells to attack a specific protein on the surface of cancer cells. The challenge is that the TME often suppresses these engineered cells before they can do their job. MC9999 gets around this by targeting PD-L1, a protein found on the surface of both the tumor cells and the immunosuppressive cells within the TME.
The strategy is explained by the researchers who developed it:
"PD-L1 is a very good target for us, because it allows us to simultaneously hit tumor cells and the immunosuppressed cells in the tumor microenvironment."
This approach is also being explored in glioblastoma, a deadly brain cancer. Researchers are mapping how immunosuppressive macrophages and glioblastoma cells co-evolve—with the macrophages changing the tumor cells and the tumor cells, in turn, changing the macrophages. This dynamic interaction creates a potent protective barrier, and by understanding it, scientists are identifying new targets on both cell types.
This represents a critical shift in immunotherapy strategy. Instead of just sending T-cells to storm the fortress (the tumor), these new therapies are designed to simultaneously dismantle the fortress walls and neutralize its guards, leaving the cancer exposed and vulnerable.
4. The "Undruggable" Is Finally Being Drugged
In oncology, some targets have been considered "undruggable" for decades. These are cancer-driving proteins whose structure and function make them incredibly difficult to block with conventional drugs. Among the most notorious of these are mutations in the RAS family of genes, which are found in a huge proportion of human cancers, including some of the deadliest. After years of effort, this frontier is finally beginning to yield.
The most prominent example of this progress is Daraxonrasib (RMC-6236), a first-of-its-kind pan-RAS inhibitor. Unlike earlier drugs that could only hit one specific type of RAS mutation, Daraxonrasib is designed to target the active form of all major RAS variants. This makes it a potential game-changer for cancers driven by this historically intractable target, particularly pancreatic ductal adenocarcinoma (PDAC), where progress has been notoriously slow.
The early results in this difficult-to-treat cancer are impressive. In patients with advanced PDAC who had already received other treatments, Daraxonrasib achieved an Objective Response Rate (ORR) of 29-35%, a median Progression-Free Survival (PFS) of approximately 8 months, and disease control rates over 90%. This translated to a median Overall Survival (OS) of 13-16 months—a level of durable benefit rarely seen in this setting. In previously untreated patients, the results were even more striking: when combined with chemotherapy, Daraxonrasib delivered an ORR of 55% and a disease control rate of approximately 90%.
The significance of these findings cannot be overstated. They demonstrate that a target long considered the "holy grail" of oncology is now vulnerable to innovative drug design. For patients with pancreatic cancer and other RAS-driven tumors, this breakthrough offers real, tangible hope where there was once very little.
5. Cancer's "Smart Bombs" Are Getting a Double-Tap Upgrade
Antibody-Drug Conjugates (ADCs) are one of the most sophisticated tools in modern oncology. They function like "smart bombs," combining a highly specific monoclonal antibody that seeks out a target on cancer cells with a potent cytotoxic payload that kills them. Now, the next generation of these smart bombs is being engineered with even greater complexity to overcome one of cancer's greatest strengths: its ability to adapt and resist treatment.
One new evolution, now in early-phase clinical trials, is the dual-payload ADC. These constructs are designed to "deliver two different cytotoxic agents simultaneously" from a single antibody. The strategic goal is to overcome drug resistance driven by tumor heterogeneity—the fact that a single tumor is often made up of different types of cells, some of which may be resistant to one type of chemotherapy but vulnerable to another.
Another powerful example of this increasing complexity is the development of bispecific ADCs, where the antibody itself is engineered to hit two targets at once. Iza-bren (izalontamab brengitecan) exemplifies this multi-pronged approach. It is a first-in-class bispecific ADC whose antibody targets two different proteins: EGFR and HER3. By co-targeting both and delivering a potent topoisomerase-I payload, Iza-bren is designed to attack the cancer’s signaling architecture and its DNA simultaneously. The power of this highly engineered weapon is clear from its practice-changing results in nasopharyngeal carcinoma, where it more than doubled the confirmed Objective Response Rate (54.6% vs 27.0%) compared to standard chemotherapy in heavily pretreated patients.
This trend shows that oncology is moving beyond single-target, single-payload drugs to create complex, multi-layered molecular weapons designed to preemptively counter cancer's most evasive tactics.
Conclusion: A Shift in Thinking
The breakthroughs of 2025 reveal a clear strategic evolution in the fight against cancer. We are moving beyond simply inhibiting the disease to a more sophisticated approach: destroying its core components, reprogramming its protective environment, preserving vital organs and functions, and deploying multi-pronged molecular weapons to overcome its defences.
These advances show that the future of oncology isn't just about better drugs, but about a fundamentally smarter, more holistic way of fighting the disease. As we continue to rewrite the biological rulebook, what long-held assumptions about cancer will be the next to fall?
